diff --git a/src/coreclr/jit/importer.cpp b/src/coreclr/jit/importer.cpp
index f6ec7f3824166..27dd18328ee7d 100644
--- a/src/coreclr/jit/importer.cpp
+++ b/src/coreclr/jit/importer.cpp
@@ -6808,6 +6808,38 @@ void Compiler::impImportAndPushBox(CORINFO_RESOLVED_TOKEN* pResolvedToken)
 
         if (varTypeIsStruct(exprToBox))
         {
+            // Workaround for GitHub issue 53549.
+            //
+            // If the struct being boxed is returned via hidden buffer and comes from an inline/gdv candidate,
+            // the IR we produce after importation is out of order:
+            //
+            //    call (&(box-temp + 8), ....)
+            //    box-temp = newobj
+            //    ret-val from call (void)
+            //        ... box-temp (on stack)
+            //
+            // For inline candidates this bad ordering gets fixed up during inlining, but for GDV candidates
+            // the GDV expansion is such that the newobj follows the call as in the above.
+            //
+            // This is nontrivial to fix in GDV, so in these (rare) cases we simply disable GDV.
+            //
+            if (exprToBox->OperIs(GT_RET_EXPR))
+            {
+                GenTreeCall* const call = exprToBox->AsRetExpr()->gtInlineCandidate->AsCall();
+
+                if (call->IsGuardedDevirtualizationCandidate() && call->HasRetBufArg())
+                {
+                    JITDUMP("Disabling GDV for [%06u] because of in-box struct return\n");
+                    call->ClearGuardedDevirtualizationCandidate();
+                    if (call->IsVirtualStub())
+                    {
+                        JITDUMP("Restoring stub addr %p from guarded devirt candidate info\n",
+                                dspPtr(call->gtGuardedDevirtualizationCandidateInfo->stubAddr));
+                        call->gtStubCallStubAddr = call->gtGuardedDevirtualizationCandidateInfo->stubAddr;
+                    }
+                }
+            }
+
             assert(info.compCompHnd->getClassSize(pResolvedToken->hClass) == info.compCompHnd->getClassSize(operCls));
             op1 = impAssignStructPtr(op1, exprToBox, operCls, (unsigned)CHECK_SPILL_ALL);
         }
diff --git a/src/tests/JIT/Regression/JitBlue/Runtime_53549/Runtime_53549.cs b/src/tests/JIT/Regression/JitBlue/Runtime_53549/Runtime_53549.cs
new file mode 100644
index 0000000000000..5078556b66446
--- /dev/null
+++ b/src/tests/JIT/Regression/JitBlue/Runtime_53549/Runtime_53549.cs
@@ -0,0 +1,49 @@
+// Licensed to the .NET Foundation under one or more agreements.
+// The .NET Foundation licenses this file to you under the MIT license.
+
+using System;
+using System.Runtime.CompilerServices;
+using System.Threading;
+
+interface I
+{
+    public Decimal F();
+}
+
+class Runtime_53549 : I
+{
+    Decimal z;
+
+    public Decimal F() => z;
+
+    public static bool G(object o) 
+    {
+        return ((decimal) o).Equals(100M);
+    }
+
+    // This method will have bad codegen if
+    // we allow GDV on i.F().
+    //
+    [MethodImpl(MethodImplOptions.NoInlining)]
+    public static int H(I i)
+    {
+        return G(i.F()) ? 100 : -1;
+    }
+
+    public static int Main()
+    {
+        Runtime_53549 x = new Runtime_53549();
+        x.z = 100M;
+
+        for (int i = 0; i < 100; i++)
+        {
+            _ = H(x);
+            Thread.Sleep(15);
+        }
+
+        return H(x);
+    }
+}
+
+
+    
diff --git a/src/tests/JIT/Regression/JitBlue/Runtime_53549/Runtime_53549.csproj b/src/tests/JIT/Regression/JitBlue/Runtime_53549/Runtime_53549.csproj
new file mode 100644
index 0000000000000..9a3423ff0d39b
--- /dev/null
+++ b/src/tests/JIT/Regression/JitBlue/Runtime_53549/Runtime_53549.csproj
@@ -0,0 +1,24 @@
+<Project Sdk="Microsoft.NET.Sdk">
+  <PropertyGroup>
+    <OutputType>Exe</OutputType>
+  </PropertyGroup>
+  <PropertyGroup>
+    <DebugType>None</DebugType>
+    <Optimize>True</Optimize>
+  </PropertyGroup>
+  <PropertyGroup>
+    <CLRTestBatchPreCommands><![CDATA[
+$(CLRTestBatchPreCommands)
+set COMPlus_TieredPGO=1
+set COMPlus_TC_QuickJitForLoops=1
+]]></CLRTestBatchPreCommands>
+    <BashCLRTestPreCommands><![CDATA[
+$(BashCLRTestPreCommands)
+export COMPlus_TieredPGO=1
+export COMPlus_TC_QuickJitForLoops=1
+]]></BashCLRTestPreCommands>
+  </PropertyGroup>
+  <ItemGroup>
+    <Compile Include="$(MSBuildProjectName).cs" />
+  </ItemGroup>
+</Project>