diff --git a/pcsx2-qt/GameList/GameListRefreshThread.cpp b/pcsx2-qt/GameList/GameListRefreshThread.cpp
index 5b3084389c..6fa5219e51 100644
--- a/pcsx2-qt/GameList/GameListRefreshThread.cpp
+++ b/pcsx2-qt/GameList/GameListRefreshThread.cpp
@@ -4,14 +4,17 @@
 #include "GameListRefreshThread.h"
 
 #include "pcsx2/GameList.h"
+#include "pcsx2/Host.h"
 
+#include "common/Assertions.h"
+#include "common/Console.h"
 #include "common/ProgressCallback.h"
-#include "common/Timer.h"
 
 #include <QtWidgets/QMessageBox>
 
-AsyncRefreshProgressCallback::AsyncRefreshProgressCallback(GameListRefreshThread* parent)
+AsyncRefreshProgressCallback::AsyncRefreshProgressCallback(bool popup_on_error, GameListRefreshThread* parent)
 	: m_parent(parent)
+	, m_popup_on_error(popup_on_error)
 {
 }
 
@@ -57,17 +60,20 @@ void AsyncRefreshProgressCallback::SetTitle(const char* title)
 
 void AsyncRefreshProgressCallback::DisplayError(const char* message)
 {
-	QMessageBox::critical(nullptr, QStringLiteral("Error"), QString::fromUtf8(message));
+	if (m_popup_on_error)
+		Host::ReportErrorAsync(TRANSLATE_SV("GameListRefreshThread", "Error"), message);
+	else
+		ERROR_LOG("{}", message);
 }
 
 void AsyncRefreshProgressCallback::DisplayWarning(const char* message)
 {
-	QMessageBox::warning(nullptr, QStringLiteral("Warning"), QString::fromUtf8(message));
+	pxFailRel("Not implemented.");
 }
 
 void AsyncRefreshProgressCallback::DisplayInformation(const char* message)
 {
-	QMessageBox::information(nullptr, QStringLiteral("Information"), QString::fromUtf8(message));
+	pxFailRel("Not implemented.");
 }
 
 void AsyncRefreshProgressCallback::DisplayDebugMessage(const char* message)
@@ -77,17 +83,18 @@ void AsyncRefreshProgressCallback::DisplayDebugMessage(const char* message)
 
 void AsyncRefreshProgressCallback::ModalError(const char* message)
 {
-	QMessageBox::critical(nullptr, QStringLiteral("Error"), QString::fromUtf8(message));
+	pxFailRel("Not implemented.");
 }
 
 bool AsyncRefreshProgressCallback::ModalConfirmation(const char* message)
 {
-	return QMessageBox::question(nullptr, QStringLiteral("Question"), QString::fromUtf8(message)) == QMessageBox::Yes;
+	pxFailRel("Not implemented.");
+	return false;
 }
 
 void AsyncRefreshProgressCallback::ModalInformation(const char* message)
 {
-	QMessageBox::information(nullptr, QStringLiteral("Information"), QString::fromUtf8(message));
+	pxFailRel("Not implemented.");
 }
 
 void AsyncRefreshProgressCallback::fireUpdate()
@@ -95,9 +102,9 @@ void AsyncRefreshProgressCallback::fireUpdate()
 	m_parent->refreshProgress(m_status_text, m_last_value, m_last_range);
 }
 
-GameListRefreshThread::GameListRefreshThread(bool invalidate_cache)
+GameListRefreshThread::GameListRefreshThread(bool invalidate_cache, bool popup_on_error)
 	: QThread()
-	, m_progress(this)
+	, m_progress(popup_on_error, this)
 	, m_invalidate_cache(invalidate_cache)
 {
 }
diff --git a/pcsx2-qt/GameList/GameListRefreshThread.h b/pcsx2-qt/GameList/GameListRefreshThread.h
index 40efd74911..a686c3dcbd 100644
--- a/pcsx2-qt/GameList/GameListRefreshThread.h
+++ b/pcsx2-qt/GameList/GameListRefreshThread.h
@@ -14,7 +14,7 @@ class GameListRefreshThread;
 class AsyncRefreshProgressCallback : public BaseProgressCallback
 {
 public:
-	AsyncRefreshProgressCallback(GameListRefreshThread* parent);
+	AsyncRefreshProgressCallback(bool popup_on_error, GameListRefreshThread* parent);
 
 	void Cancel();
 
@@ -38,6 +38,7 @@ private:
 	QString m_status_text;
 	int m_last_range = 1;
 	int m_last_value = 0;
+	bool m_popup_on_error = false;
 };
 
 class GameListRefreshThread final : public QThread
@@ -45,7 +46,7 @@ class GameListRefreshThread final : public QThread
 	Q_OBJECT
 
 public:
-	GameListRefreshThread(bool invalidate_cache);
+	GameListRefreshThread(bool invalidate_cache, bool popup_on_error);
 	~GameListRefreshThread();
 
 	void cancel();
@@ -60,4 +61,5 @@ protected:
 private:
 	AsyncRefreshProgressCallback m_progress;
 	bool m_invalidate_cache;
+	bool m_popup_on_error;
 };
diff --git a/pcsx2-qt/GameList/GameListWidget.cpp b/pcsx2-qt/GameList/GameListWidget.cpp
index ccd80b7758..7c3b5b7d6b 100644
--- a/pcsx2-qt/GameList/GameListWidget.cpp
+++ b/pcsx2-qt/GameList/GameListWidget.cpp
@@ -294,7 +294,7 @@ void GameListWidget::initialize()
 	m_empty_ui.setupUi(m_empty_widget);
 	m_empty_ui.supportedFormats->setText(qApp->translate("GameListWidget", SUPPORTED_FORMATS_STRING));
 	connect(m_empty_ui.addGameDirectory, &QPushButton::clicked, this, [this]() { emit addGameDirectoryRequested(); });
-	connect(m_empty_ui.scanForNewGames, &QPushButton::clicked, this, [this]() { refresh(false); });
+	connect(m_empty_ui.scanForNewGames, &QPushButton::clicked, this, [this]() { refresh(false, true); });
 	connect(qApp, &QGuiApplication::applicationStateChanged, this, [this]() { GameListWidget::updateCustomBackgroundState(); });
 	m_ui.stack->insertWidget(2, m_empty_widget);
 
@@ -453,11 +453,11 @@ bool GameListWidget::getShowGridCoverTitles() const
 	return m_model->getShowCoverTitles();
 }
 
-void GameListWidget::refresh(bool invalidate_cache)
+void GameListWidget::refresh(bool invalidate_cache, bool popup_on_error)
 {
 	cancelRefresh();
 
-	m_refresh_thread = new GameListRefreshThread(invalidate_cache);
+	m_refresh_thread = new GameListRefreshThread(invalidate_cache, popup_on_error);
 	connect(m_refresh_thread, &GameListRefreshThread::refreshProgress, this, &GameListWidget::onRefreshProgress,
 		Qt::QueuedConnection);
 	connect(m_refresh_thread, &GameListRefreshThread::refreshComplete, this, &GameListWidget::onRefreshComplete,
diff --git a/pcsx2-qt/GameList/GameListWidget.h b/pcsx2-qt/GameList/GameListWidget.h
index 7a061f8b07..7043fbba1e 100644
--- a/pcsx2-qt/GameList/GameListWidget.h
+++ b/pcsx2-qt/GameList/GameListWidget.h
@@ -46,7 +46,7 @@ public:
 	void initialize();
 	void resizeTableViewColumnsToFit();
 
-	void refresh(bool invalidate_cache);
+	void refresh(bool invalidate_cache, bool popup_on_error);
 	void cancelRefresh();
 	void reloadThemeSpecificImages();
 	void setCustomBackground(bool force = false);
diff --git a/pcsx2-qt/MainWindow.cpp b/pcsx2-qt/MainWindow.cpp
index 2070271b09..826a164d5d 100644
--- a/pcsx2-qt/MainWindow.cpp
+++ b/pcsx2-qt/MainWindow.cpp
@@ -357,8 +357,8 @@ void MainWindow::connectSignals()
 		[this]() { doControllerSettings(ControllerSettingsWindow::Category::HotkeySettings); });
 	connect(m_ui.actionAddGameDirectory, &QAction::triggered,
 		[this]() { getSettingsWindow()->getGameListSettingsWidget()->addSearchDirectory(this); });
-	connect(m_ui.actionScanForNewGames, &QAction::triggered, [this]() { refreshGameList(false); });
-	connect(m_ui.actionRescanAllGames, &QAction::triggered, [this]() { refreshGameList(true); });
+	connect(m_ui.actionScanForNewGames, &QAction::triggered, [this]() { refreshGameList(false, true); });
+	connect(m_ui.actionRescanAllGames, &QAction::triggered, [this]() { refreshGameList(true, true); });
 	connect(m_ui.actionViewToolbar, &QAction::toggled, this, &MainWindow::onViewToolbarActionToggled);
 	connect(m_ui.actionViewLockToolbar, &QAction::toggled, this, &MainWindow::onViewLockToolbarActionToggled);
 	connect(m_ui.actionViewStatusBar, &QAction::toggled, this, &MainWindow::onViewStatusBarActionToggled);
@@ -547,7 +547,7 @@ void MainWindow::recreate()
 	MainWindow* new_main_window = new MainWindow();
 	pxAssert(g_main_window == new_main_window);
 	new_main_window->initialize();
-	new_main_window->refreshGameList(false);
+	new_main_window->refreshGameList(false, false);
 	new_main_window->show();
 	deleteLater();
 
@@ -1137,7 +1137,7 @@ bool MainWindow::shouldMouseLock() const
 	if (!Host::GetBoolSettingValue("EmuCore", "EnableMouseLock", false))
 		return false;
 
-	if(m_display_created == false || m_display_widget == nullptr && !isRenderingToMain())
+	if (m_display_created == false || m_display_widget == nullptr && !isRenderingToMain())
 		return false;
 
 	bool windowsHidden = (!g_debugger_window || g_debugger_window->isHidden()) &&
@@ -1146,7 +1146,7 @@ bool MainWindow::shouldMouseLock() const
 
 	auto* displayWindow = isRenderingToMain() ? window() : m_display_widget->window();
 
-	if(displayWindow == nullptr)
+	if (displayWindow == nullptr)
 		return false;
 
 	return windowsHidden && (displayWindow->isActiveWindow() || displayWindow->isFullScreen());
@@ -1215,13 +1215,9 @@ void MainWindow::switchToEmulationView()
 		m_display_widget->setFocus();
 }
 
-void MainWindow::refreshGameList(bool invalidate_cache)
+void MainWindow::refreshGameList(bool invalidate_cache, bool popup_on_error)
 {
-	// can't do this while the VM is running because of CDVD
-	if (s_vm_valid)
-		return;
-
-	m_game_list_widget->refresh(invalidate_cache);
+	m_game_list_widget->refresh(invalidate_cache, popup_on_error);
 }
 
 void MainWindow::cancelGameListRefresh()
@@ -1466,8 +1462,7 @@ void MainWindow::onGameListEntryContextMenuRequested(const QPoint& point)
 		const time_t entry_played_time = GameList::GetCachedPlayedTimeForSerial(entry->serial);
 		// Best two options given zero play time are to grey this out or to not show it at all.
 		if (entry_played_time)
-			connect(menu.addAction(tr("Reset Play Time")), &QAction::triggered, [this, entry, entry_played_time]()
-				{ clearGameListEntryPlayTime(entry, entry_played_time); });
+			connect(menu.addAction(tr("Reset Play Time")), &QAction::triggered, [this, entry, entry_played_time]() { clearGameListEntryPlayTime(entry, entry_played_time); });
 
 		// Check Wiki Page functionality is based on a serial redirect.
 		if (!entry->serial.empty())
@@ -2102,7 +2097,7 @@ void MainWindow::onVMStopped()
 
 	// reload played time
 	if (m_game_list_widget->isShowingGameList())
-		m_game_list_widget->refresh(false);
+		m_game_list_widget->refresh(false, false);
 }
 
 void MainWindow::onGameChanged(const QString& title, const QString& elf_override, const QString& disc_path,
@@ -2932,12 +2927,12 @@ void MainWindow::clearGameListEntryPlayTime(const GameList::Entry* entry, const
 	if (QMessageBox::question(this, tr("Confirm Reset"),
 			tr("Are you sure you want to reset the play time for '%1' (%2)?\n\nYour current play time is %3.\n\nThis action cannot be undone.")
 				.arg(entry->title.empty() ? tr("empty title") : QString::fromStdString(entry->title),
-					 entry->serial.empty() ? tr("no serial") : QString::fromStdString(entry->serial),
-					 QString::fromStdString(GameList::FormatTimespan(entry_played_time, true))),
-					 (QMessageBox::Yes | QMessageBox::No), QMessageBox::No) == QMessageBox::Yes)
+					entry->serial.empty() ? tr("no serial") : QString::fromStdString(entry->serial),
+					QString::fromStdString(GameList::FormatTimespan(entry_played_time, true))),
+			(QMessageBox::Yes | QMessageBox::No), QMessageBox::No) == QMessageBox::Yes)
 	{
 		GameList::ClearPlayedTimeForSerial(entry->serial);
-		m_game_list_widget->refresh(false);
+		m_game_list_widget->refresh(false, false);
 	}
 }
 
diff --git a/pcsx2-qt/MainWindow.h b/pcsx2-qt/MainWindow.h
index f86240c3f7..b9f8e5c36d 100644
--- a/pcsx2-qt/MainWindow.h
+++ b/pcsx2-qt/MainWindow.h
@@ -113,7 +113,7 @@ public:
 	void checkMousePosition(int x, int y);
 public Q_SLOTS:
 	void checkForUpdates(bool display_message, bool force_check);
-	void refreshGameList(bool invalidate_cache);
+	void refreshGameList(bool invalidate_cache, bool popup_on_error);
 	void cancelGameListRefresh();
 	void reportInfo(const QString& title, const QString& message);
 	void reportError(const QString& title, const QString& message);
diff --git a/pcsx2-qt/QtHost.cpp b/pcsx2-qt/QtHost.cpp
index a65fbd08d5..c3025f48c3 100644
--- a/pcsx2-qt/QtHost.cpp
+++ b/pcsx2-qt/QtHost.cpp
@@ -1152,7 +1152,7 @@ void Host::OpenHostFileSelectorAsync(std::string_view title, bool select_directo
 	if (!filters.empty())
 	{
 		filters_str.append(QStringLiteral("All File Types (%1)")
-				.arg(QString::fromStdString(StringUtil::JoinString(filters.begin(), filters.end(), " "))));
+							   .arg(QString::fromStdString(StringUtil::JoinString(filters.begin(), filters.end(), " "))));
 		for (const std::string& filter : filters)
 		{
 			filters_str.append(
@@ -2385,7 +2385,7 @@ int main(int argc, char* argv[])
 
 	// When running in batch mode, ensure game list is loaded, but don't scan for any new files.
 	if (!s_batch_mode)
-		g_main_window->refreshGameList(false);
+		g_main_window->refreshGameList(false, false);
 	else
 		GameList::Refresh(false, true);
 
diff --git a/pcsx2-qt/Settings/GameListSettingsWidget.cpp b/pcsx2-qt/Settings/GameListSettingsWidget.cpp
index 63395e679a..378cc6e55c 100644
--- a/pcsx2-qt/Settings/GameListSettingsWidget.cpp
+++ b/pcsx2-qt/Settings/GameListSettingsWidget.cpp
@@ -63,7 +63,7 @@ bool GameListSettingsWidget::addExcludedPath(const std::string& path)
 
 	Host::CommitBaseSettingChanges();
 	m_ui.excludedPaths->addItem(QString::fromStdString(path));
-	g_main_window->refreshGameList(false);
+	g_main_window->refreshGameList(false, true);
 	return true;
 }
 
@@ -152,7 +152,7 @@ void GameListSettingsWidget::addSearchDirectory(const QString& path, bool recurs
 	Host::AddBaseValueToStringList("GameList", recursive ? "RecursivePaths" : "Paths", spath.c_str());
 	Host::CommitBaseSettingChanges();
 	refreshDirectoryList();
-	g_main_window->refreshGameList(false);
+	g_main_window->refreshGameList(false, true);
 }
 
 void GameListSettingsWidget::removeSearchDirectory(const QString& path)
@@ -166,7 +166,7 @@ void GameListSettingsWidget::removeSearchDirectory(const QString& path)
 
 	Host::CommitBaseSettingChanges();
 	refreshDirectoryList();
-	g_main_window->refreshGameList(false);
+	g_main_window->refreshGameList(false, true);
 }
 
 void GameListSettingsWidget::onDirectoryListContextMenuRequested(const QPoint& point)
@@ -261,7 +261,7 @@ void GameListSettingsWidget::onRemoveExcludedPathButtonClicked()
 
 	delete item;
 
-	g_main_window->refreshGameList(false);
+	g_main_window->refreshGameList(false, true);
 }
 
 void GameListSettingsWidget::onExcludedPathsSelectionChanged()
@@ -271,10 +271,10 @@ void GameListSettingsWidget::onExcludedPathsSelectionChanged()
 
 void GameListSettingsWidget::onRescanAllGamesClicked()
 {
-	g_main_window->refreshGameList(true);
+	g_main_window->refreshGameList(true, true);
 }
 
 void GameListSettingsWidget::onScanForNewGamesClicked()
 {
-	g_main_window->refreshGameList(false);
+	g_main_window->refreshGameList(false, true);
 }
diff --git a/pcsx2-qt/Settings/GameSummaryWidget.cpp b/pcsx2-qt/Settings/GameSummaryWidget.cpp
index 2f6248426a..9312356d3b 100644
--- a/pcsx2-qt/Settings/GameSummaryWidget.cpp
+++ b/pcsx2-qt/Settings/GameSummaryWidget.cpp
@@ -280,7 +280,8 @@ void GameSummaryWidget::onVerifyClicked()
 	Error error;
 	if (!hasher.Open(m_entry_path, &error))
 	{
-		setVerifyResult(QString::fromStdString(error.GetDescription()));
+		QString message(QString::fromStdString(error.GetDescription()));
+		QMessageBox::critical(QtUtils::GetRootWidget(this), tr("Error"), message);
 		return;
 	}
 
diff --git a/pcsx2/CDVD/CDVDcommon.cpp b/pcsx2/CDVD/CDVDcommon.cpp
index d5cd11ed44..a4a40e11bf 100644
--- a/pcsx2/CDVD/CDVDcommon.cpp
+++ b/pcsx2/CDVD/CDVDcommon.cpp
@@ -21,6 +21,7 @@
 #include <ctype.h>
 #include <exception>
 #include <memory>
+#include <mutex>
 #include <time.h>
 
 #include "fmt/format.h"
@@ -270,6 +271,23 @@ static void DetectDiskType()
 
 static std::string m_SourceFilename[3];
 static CDVD_SourceType m_CurrentSourceType = CDVD_SourceType::NoDisc;
+static std::mutex s_cdvd_lock;
+
+bool cdvdLock(Error* error)
+{
+	if (!s_cdvd_lock.try_lock())
+	{
+		Error::SetString(error, TRANSLATE_STR("CDVD", "The CDVD system is currently in use."));
+		return false;
+	}
+
+	return true;
+}
+
+void cdvdUnlock()
+{
+	s_cdvd_lock.unlock();
+}
 
 void CDVDsys_SetFile(CDVD_SourceType srctype, std::string newfile)
 {
@@ -579,7 +597,7 @@ static s32 NODISCdummyS32()
 	return 0;
 }
 
-static void NODISCnewDiskCB(void (*/* callback */)())
+static void NODISCnewDiskCB(void (* /* callback */)())
 {
 }
 
diff --git a/pcsx2/CDVD/CDVDcommon.h b/pcsx2/CDVD/CDVDcommon.h
index 1e74232ad6..6bd9ead3ad 100644
--- a/pcsx2/CDVD/CDVDcommon.h
+++ b/pcsx2/CDVD/CDVDcommon.h
@@ -20,7 +20,6 @@ struct cdvdTrackIndex
 	u8 discM; // current minute location on the disc (BCD encoded)
 	u8 discS; // current sector location on the disc (BCD encoded)
 	u8 discF; // current frame location on the disc (BCD encoded)
-
 };
 
 struct cdvdTrack
@@ -188,6 +187,13 @@ extern u8 strack;
 extern u8 etrack;
 extern std::array<cdvdTrack, 100> tracks;
 
+/// Try to take the CDVD lock, return false if it's already in use.
+/// Must be called before your first CDVD call.
+extern bool cdvdLock(Error* error = nullptr);
+
+/// Release the CDVD lock. Must be called after you're done with CDVD.
+extern void cdvdUnlock();
+
 extern void CDVDsys_ChangeSource(CDVD_SourceType type);
 extern void CDVDsys_SetFile(CDVD_SourceType srctype, std::string newfile);
 extern const std::string& CDVDsys_GetFile(CDVD_SourceType srctype);
diff --git a/pcsx2/CDVD/IsoHasher.cpp b/pcsx2/CDVD/IsoHasher.cpp
index a66dcece1a..98428f3824 100644
--- a/pcsx2/CDVD/IsoHasher.cpp
+++ b/pcsx2/CDVD/IsoHasher.cpp
@@ -7,7 +7,6 @@
 
 #include "common/Error.h"
 #include "common/MD5Digest.h"
-#include "common/StringUtil.h"
 
 #include "fmt/format.h"
 
@@ -39,6 +38,10 @@ bool IsoHasher::Open(std::string iso_path, Error* error)
 {
 	Close();
 
+	m_is_locked = cdvdLock(error);
+	if (!m_is_locked)
+		return false;
+
 	CDVDsys_SetFile(CDVD_SourceType::Iso, std::move(iso_path));
 	CDVDsys_ChangeSource(CDVD_SourceType::Iso);
 
@@ -103,6 +106,12 @@ bool IsoHasher::Open(std::string iso_path, Error* error)
 
 void IsoHasher::Close()
 {
+	if (!m_is_locked)
+		return;
+
+	cdvdUnlock();
+	m_is_locked = false;
+
 	if (!m_is_open)
 		return;
 
@@ -151,7 +160,7 @@ bool IsoHasher::ComputeTrackHash(Track& track, ProgressCallback* callback)
 	const u32 update_interval = std::max<u32>(track.sectors / 100u, 1u);
 	callback->SetStatusText(
 		fmt::format(TRANSLATE_FS("CDVD", "Calculating checksum for track {}..."), track.number).c_str());
-    callback->SetProgressRange(track.sectors);
+	callback->SetProgressRange(track.sectors);
 
 	MD5Digest md5;
 	for (u32 i = 0; i < track.sectors; i++)
diff --git a/pcsx2/CDVD/IsoHasher.h b/pcsx2/CDVD/IsoHasher.h
index bb7f3dacec..991f26ac6c 100644
--- a/pcsx2/CDVD/IsoHasher.h
+++ b/pcsx2/CDVD/IsoHasher.h
@@ -28,6 +28,9 @@ public:
 	IsoHasher();
 	~IsoHasher();
 
+	IsoHasher(const IsoHasher&) = delete;
+	IsoHasher& operator=(const IsoHasher&) = delete;
+
 	static std::string_view GetTrackTypeString(u32 type);
 
 	u32 GetTrackCount() const { return static_cast<u32>(m_tracks.size()); }
@@ -44,6 +47,7 @@ private:
 	bool ComputeTrackHash(Track& track, ProgressCallback* callback);
 
 	std::vector<Track> m_tracks;
+	bool m_is_locked = false;
 	bool m_is_open = false;
 	bool m_is_cd = false;
 };
diff --git a/pcsx2/DebugTools/SymbolImporter.cpp b/pcsx2/DebugTools/SymbolImporter.cpp
index e054954c4c..e4785f09d8 100644
--- a/pcsx2/DebugTools/SymbolImporter.cpp
+++ b/pcsx2/DebugTools/SymbolImporter.cpp
@@ -163,6 +163,9 @@ void SymbolImporter::Reset()
 
 void SymbolImporter::LoadAndAnalyseElf(Pcsx2Config::DebugAnalysisOptions options)
 {
+	if (!VMManager::HasValidVM())
+		return;
+
 	const std::string& elf_path = VMManager::GetCurrentELF();
 
 	Error error;
@@ -192,6 +195,9 @@ void SymbolImporter::AnalyseElf(
 	Pcsx2Config::DebugAnalysisOptions options,
 	bool wait_until_elf_is_loaded)
 {
+	if (!VMManager::HasValidVM())
+		return;
+
 	// Search for a .sym file to load symbols from.
 	std::string nocash_path;
 	CDVD_SourceType source_type = CDVDsys_GetSourceType();
diff --git a/pcsx2/GameList.cpp b/pcsx2/GameList.cpp
index 1b5b7535cd..ab3f9ffe92 100644
--- a/pcsx2/GameList.cpp
+++ b/pcsx2/GameList.cpp
@@ -16,6 +16,7 @@
 #include "common/HeterogeneousContainers.h"
 #include "common/Path.h"
 #include "common/ProgressCallback.h"
+#include "common/ScopedGuard.h"
 #include "common/StringUtil.h"
 
 #include <algorithm>
@@ -826,6 +827,15 @@ void GameList::Refresh(bool invalidate_cache, bool only_cache, ProgressCallback*
 	if (!progress)
 		progress = ProgressCallback::NullProgressCallback;
 
+	Error cdvd_lock_error;
+	if (!cdvdLock(&cdvd_lock_error))
+	{
+		progress->DisplayError(cdvd_lock_error.GetDescription().c_str());
+		return;
+	}
+
+	ScopedGuard unlock_cdvd = &cdvdUnlock;
+
 	if (invalidate_cache)
 		DeleteCacheFile();
 	else
diff --git a/pcsx2/VMManager.cpp b/pcsx2/VMManager.cpp
index 12153807f0..f55cddcba4 100644
--- a/pcsx2/VMManager.cpp
+++ b/pcsx2/VMManager.cpp
@@ -485,7 +485,7 @@ void VMManager::UpdateLoggingSettings(SettingsInterface& si)
 	if (system_console_enabled != Log::IsConsoleOutputEnabled())
 		Log::SetConsoleOutputLevel(system_console_enabled ? level : LOGLEVEL_NONE);
 
-	// Debug console only exists on Windows.
+		// Debug console only exists on Windows.
 #ifdef _WIN32
 	const bool debug_console_enabled = IsDebuggerPresent() && si.GetBoolValue("Logging", "EnableDebugConsole", false);
 	Log::SetDebugOutputLevel(debug_console_enabled ? level : LOGLEVEL_NONE);
@@ -776,8 +776,8 @@ std::string VMManager::GetGameSettingsPath(const std::string_view game_serial, u
 	std::string sanitized_serial(Path::SanitizeFileName(game_serial));
 
 	return game_serial.empty() ?
-			   Path::Combine(EmuFolders::GameSettings, fmt::format("{:08X}.ini", game_crc)) :
-			   Path::Combine(EmuFolders::GameSettings, fmt::format("{}_{:08X}.ini", sanitized_serial, game_crc));
+	           Path::Combine(EmuFolders::GameSettings, fmt::format("{:08X}.ini", game_crc)) :
+	           Path::Combine(EmuFolders::GameSettings, fmt::format("{}_{:08X}.ini", sanitized_serial, game_crc));
 }
 
 std::string VMManager::GetDiscOverrideFromGameSettings(const std::string& elf_path)
@@ -1324,6 +1324,15 @@ bool VMManager::Initialize(VMBootParameters boot_params)
 		}
 	}
 
+	Error cdvd_lock_error;
+	if (!cdvdLock(&cdvd_lock_error))
+	{
+		Host::ReportErrorAsync("Startup Error", cdvd_lock_error.GetDescription());
+		return false;
+	}
+
+	ScopedGuard unlock_cdvd = &cdvdUnlock;
+
 	// resolve source type
 	if (boot_params.source_type.has_value())
 	{
@@ -1355,12 +1364,14 @@ bool VMManager::Initialize(VMBootParameters boot_params)
 		if (!LoadBIOS())
 		{
 			Host::ReportErrorAsync(TRANSLATE_SV("VMManager", "Error – No BIOS Present"),
-				fmt::format(TRANSLATE_FS("VMManager",
-					"PCSX2 requires a PlayStation 2 BIOS in order to run.\n\n"
-					"For legal reasons, you will need to obtain this BIOS from a PlayStation 2 unit which you own.\n\n"
-					"For step-by-step help with this process, please consult the setup guide at {}.\n\n"
-					"PCSX2 will be able to run once you've placed your BIOS image inside the folder named \"bios\" within the data directory "
-					"(Tools Menu -> Open Data Directory)."), PCSX2_DOCUMENTATION_BIOS_URL_SHORTENED));
+				fmt::format(
+					TRANSLATE_FS("VMManager",
+						"PCSX2 requires a PlayStation 2 BIOS in order to run.\n\n"
+						"For legal reasons, you will need to obtain this BIOS from a PlayStation 2 unit which you own.\n\n"
+						"For step-by-step help with this process, please consult the setup guide at {}.\n\n"
+						"PCSX2 will be able to run once you've placed your BIOS image inside the folder named \"bios\" within the data directory "
+						"(Tools Menu -> Open Data Directory)."),
+					PCSX2_DOCUMENTATION_BIOS_URL_SHORTENED));
 			return false;
 		}
 
@@ -1559,6 +1570,7 @@ bool VMManager::Initialize(VMBootParameters boot_params)
 	close_memcards.Cancel();
 	close_cdvd.Cancel();
 	close_cdvd_files.Cancel();
+	unlock_cdvd.Cancel();
 	close_state.Cancel();
 
 	if (EmuConfig.CdvdPrecache)
@@ -1667,6 +1679,8 @@ void VMManager::Shutdown(bool save_resume_state)
 	else
 		cdvdSaveNVRAM();
 
+	cdvdUnlock();
+
 	s_state.store(VMState::Shutdown, std::memory_order_release);
 	FullscreenUI::OnVMDestroyed();
 	SaveStateSelectorUI::Clear();