diff --git a/src/coreclr/jit/codegencommon.cpp b/src/coreclr/jit/codegencommon.cpp
index dcf1768c60a7d..f3e2566330da6 100644
--- a/src/coreclr/jit/codegencommon.cpp
+++ b/src/coreclr/jit/codegencommon.cpp
@@ -12551,6 +12551,17 @@ void CodeGen::genPoisonFrame(regMaskTP regLiveIn)
 
         assert(varDsc->lvOnFrame);
 
+        int size = (int)compiler->lvaLclSize(varNum);
+
+        if ((size / TARGET_POINTER_SIZE) > 16)
+        {
+            // For very large structs the offsets in the movs we emit below can
+            // grow too large to be handled properly by JIT. Furthermore, while
+            // this is only debug code, for very large structs this can bloat
+            // the code too much due to the singular movs used.
+            continue;
+        }
+
         if (!hasPoisonImm)
         {
 #ifdef TARGET_64BIT
@@ -12568,8 +12579,7 @@ void CodeGen::genPoisonFrame(regMaskTP regLiveIn)
 #else
         int addr = 0;
 #endif
-        int size = (int)compiler->lvaLclSize(varNum);
-        int end  = addr + size;
+        int end = addr + size;
         for (int offs = addr; offs < end;)
         {
 #ifdef TARGET_64BIT
diff --git a/src/tests/JIT/Directed/debugging/poison.cs b/src/tests/JIT/Directed/debugging/poison.cs
index 463894a4e6a35..81c669a803728 100644
--- a/src/tests/JIT/Directed/debugging/poison.cs
+++ b/src/tests/JIT/Directed/debugging/poison.cs
@@ -19,6 +19,24 @@ public static unsafe int Main()
         WithoutGCRef poisoned2;
         Unsafe.SkipInit(out poisoned2);
         result &= VerifyPoison(&poisoned2, sizeof(WithoutGCRef));
+        
+        Massive notPoisoned;
+        Unsafe.SkipInit(out notPoisoned);
+        // too large to be poisoned, just expose it but don't check return value
+        VerifyPoison(&notPoisoned, sizeof(Massive));
+
+        WithoutGCRef poisoned4;
+        Unsafe.SkipInit(out poisoned4);
+        result &= VerifyPoison(&poisoned4, sizeof(WithoutGCRef));
+
+        Massive notPoisoned2;
+        Unsafe.SkipInit(out notPoisoned2);
+        // too large to be poisoned, just expose it but don't check return value
+        VerifyPoison(&notPoisoned2, sizeof(Massive));
+
+        GCRef zeroed2;
+        Unsafe.SkipInit(out zeroed2);
+        result &= VerifyZero(Unsafe.AsPointer(ref zeroed2), Unsafe.SizeOf<GCRef>());
 
         return result ? 100 : 101;
     }
@@ -53,4 +71,9 @@ private struct WithoutGCRef
         public int ANumber;
         public float AFloat;
     }
-}
+    
+    private unsafe struct Massive
+    {
+        public fixed byte Bytes[0x10008];
+    }
+}
\ No newline at end of file