diff --git a/Misc/NEWS.d/next/Windows/2021-12-06-14-25-05.bpo-45582.sCqL7u.rst b/Misc/NEWS.d/next/Windows/2021-12-06-14-25-05.bpo-45582.sCqL7u.rst
new file mode 100644
index 00000000000000..517015b48add90
--- /dev/null
+++ b/Misc/NEWS.d/next/Windows/2021-12-06-14-25-05.bpo-45582.sCqL7u.rst
@@ -0,0 +1,5 @@
+When PGO building on Windows, the folder for the instrumented binaries is
+now located at the same level as that for the production builds.
+(e.g. ``PCbuild/amd64/instrumented`` to ``PCbuild/amd64_instrumented``)
+We need to follow ``VPATH``, which is used in new ``getpath.py`` and defined as
+``"..\\.."`` in ``pythoncore.vcxproj``, to calculate the correct prefix folder.
diff --git a/PCbuild/pyproject.props b/PCbuild/pyproject.props
index 0eaeb6b1229a26..bf3bb904231622 100644
--- a/PCbuild/pyproject.props
+++ b/PCbuild/pyproject.props
@@ -158,8 +158,8 @@ public override bool Execute() {
 
   <Target Name="CopyPGCFiles" BeforeTargets="PrepareForBuild" Condition="$(Configuration) == 'PGUpdate'">
     <ItemGroup>
-      <_PGCFiles Include="$(OutDir)instrumented\$(TargetName)!*.pgc" />
-      <_PGDFile Include="$(OutDir)instrumented\$(TargetName).pgd" />
+      <_PGCFiles Include="$(OutDir.TrimEnd('\'))_instrumented\$(TargetName)!*.pgc" />
+      <_PGDFile Include="$(OutDir.TrimEnd('\'))_instrumented\$(TargetName).pgd" />
       <_CopyFiles Include="@(_PGCFiles);@(_PGDFile)" Condition="Exists(%(FullPath))" />
     </ItemGroup>
     <Delete Files="@(_CopyFiles->'$(OutDir)%(Filename)%(Extension)')" />
diff --git a/PCbuild/python.props b/PCbuild/python.props
index 7b85ad1c94f16e..b30c9db0a19547 100644
--- a/PCbuild/python.props
+++ b/PCbuild/python.props
@@ -51,7 +51,7 @@
     <BuildPath Condition="'$(ArchName)' == 'arm64'">$(BuildPathArm64)</BuildPath>
     <BuildPath Condition="'$(BuildPath)' == ''">$(PySourcePath)PCbuild\$(ArchName)\</BuildPath>
     <BuildPath Condition="!HasTrailingSlash($(BuildPath))">$(BuildPath)\</BuildPath>
-    <BuildPath Condition="$(Configuration) == 'PGInstrument'">$(BuildPath)instrumented\</BuildPath>
+    <BuildPath Condition="$(Configuration) == 'PGInstrument'">$(BuildPath.TrimEnd('\'))_instrumented\</BuildPath>
     
     <!-- Directories of external projects. tcltk is handled in tcltk.props -->
     <ExternalsDir>$(EXTERNALS_DIR)</ExternalsDir>