diff --git a/Source/Core/Core/PowerPC/BreakPoints.cpp b/Source/Core/Core/PowerPC/BreakPoints.cpp
index 1fef4e4e25..c933348eaf 100644
--- a/Source/Core/Core/PowerPC/BreakPoints.cpp
+++ b/Source/Core/Core/PowerPC/BreakPoints.cpp
@@ -306,9 +306,13 @@ void MemChecks::Add(TMemCheck memory_check)
   {
     m_mem_checks.emplace_back(std::move(memory_check));
   }
-  // If this is the first one, clear the JIT cache so it can switch to
-  // watchpoint-compatible code.
-  if (!had_any)
+
+  const bool registers_changed = UpdateRegistersUsedInConditions();
+
+  // If this is the first memcheck, clear the JIT cache so it can switch to watchpoint-compatible
+  // code. Or, if the memcheck's condition wants to read from a new register,
+  // clear the JIT cache to make the slow memory access code flush that register.
+  if (!had_any || registers_changed)
     m_system.GetJitInterface().ClearCache(guard);
   m_system.GetMMU().DBATUpdated();
 }
@@ -336,7 +340,10 @@ bool MemChecks::Remove(u32 address)
 
   const Core::CPUThreadGuard guard(m_system);
   m_mem_checks.erase(iter);
-  if (!HasAny())
+
+  const bool registers_changed = UpdateRegistersUsedInConditions();
+
+  if (registers_changed || !HasAny())
     m_system.GetJitInterface().ClearCache(guard);
   m_system.GetMMU().DBATUpdated();
   return true;
@@ -379,6 +386,27 @@ bool MemChecks::OverlapsMemcheck(u32 address, u32 length) const
   });
 }
 
+bool MemChecks::UpdateRegistersUsedInConditions()
+{
+  BitSet32 gprs_used, fprs_used;
+  for (TMemCheck& mem_check : m_mem_checks)
+  {
+    if (mem_check.condition)
+    {
+      gprs_used |= mem_check.condition->GetGPRsUsed();
+      fprs_used |= mem_check.condition->GetFPRsUsed();
+    }
+  }
+
+  const bool registers_changed =
+      gprs_used != m_gprs_used_in_conditions || fprs_used != m_fprs_used_in_conditions;
+
+  m_gprs_used_in_conditions = gprs_used;
+  m_fprs_used_in_conditions = fprs_used;
+
+  return registers_changed;
+}
+
 bool TMemCheck::Action(Core::System& system, u64 value, u32 addr, bool write, size_t size, u32 pc)
 {
   if (!is_enabled)
diff --git a/Source/Core/Core/PowerPC/BreakPoints.h b/Source/Core/Core/PowerPC/BreakPoints.h
index 9b07fb53c0..e48def944b 100644
--- a/Source/Core/Core/PowerPC/BreakPoints.h
+++ b/Source/Core/Core/PowerPC/BreakPoints.h
@@ -8,6 +8,7 @@
 #include <string>
 #include <vector>
 
+#include "Common/BitSet.h"
 #include "Common/CommonTypes.h"
 #include "Core/PowerPC/Expression.h"
 
@@ -127,7 +128,15 @@ public:
   void Clear();
   bool HasAny() const { return !m_mem_checks.empty(); }
 
+  BitSet32 GetGPRsUsedInConditions() { return m_gprs_used_in_conditions; }
+  BitSet32 GetFPRsUsedInConditions() { return m_fprs_used_in_conditions; }
+
 private:
+  // Returns whether any change was made
+  bool UpdateRegistersUsedInConditions();
+
   TMemChecks m_mem_checks;
   Core::System& m_system;
+  BitSet32 m_gprs_used_in_conditions;
+  BitSet32 m_fprs_used_in_conditions;
 };
diff --git a/Source/Core/Core/PowerPC/Expression.cpp b/Source/Core/Core/PowerPC/Expression.cpp
index a05fa2c8b2..38b003a806 100644
--- a/Source/Core/Core/PowerPC/Expression.cpp
+++ b/Source/Core/Core/PowerPC/Expression.cpp
@@ -495,3 +495,22 @@ std::string Expression::GetText() const
 {
   return m_text;
 }
+
+void Expression::ComputeRegistersUsed()
+{
+  if (m_has_computed_registers_used)
+    return;
+
+  for (const VarBinding& bind : m_binds)
+  {
+    switch (bind.type)
+    {
+    case VarBindingType::GPR:
+      m_gprs_used[bind.index] = true;
+      break;
+    case VarBindingType::FPR:
+      m_fprs_used[bind.index] = true;
+      break;
+    }
+  }
+}
diff --git a/Source/Core/Core/PowerPC/Expression.h b/Source/Core/Core/PowerPC/Expression.h
index 3c439f9e9e..deee9e69ad 100644
--- a/Source/Core/Core/PowerPC/Expression.h
+++ b/Source/Core/Core/PowerPC/Expression.h
@@ -9,6 +9,8 @@
 #include <string_view>
 #include <vector>
 
+#include "Common/BitSet.h"
+
 struct expr;
 struct expr_var_list;
 
@@ -41,6 +43,18 @@ public:
 
   std::string GetText() const;
 
+  BitSet32 GetGPRsUsed()
+  {
+    ComputeRegistersUsed();
+    return m_gprs_used;
+  }
+
+  BitSet32 GetFPRsUsed()
+  {
+    ComputeRegistersUsed();
+    return m_fprs_used;
+  }
+
 private:
   enum class SynchronizeDirection
   {
@@ -69,10 +83,16 @@ private:
   void SynchronizeBindings(Core::System& system, SynchronizeDirection dir) const;
   void Reporting(const double result) const;
 
+  void ComputeRegistersUsed();
+
   std::string m_text;
   ExprPointer m_expr;
   ExprVarListPointer m_vars;
   std::vector<VarBinding> m_binds;
+
+  BitSet32 m_gprs_used;
+  BitSet32 m_fprs_used;
+  bool m_has_computed_registers_used = false;
 };
 
 inline bool EvaluateCondition(Core::System& system, const std::optional<Expression>& condition)