diff --git a/clang/lib/Lex/PPMacroExpansion.cpp b/clang/lib/Lex/PPMacroExpansion.cpp
--- a/clang/lib/Lex/PPMacroExpansion.cpp
+++ b/clang/lib/Lex/PPMacroExpansion.cpp
@@ -820,18 +820,26 @@
         }
       } else if (Tok.is(tok::l_paren)) {
         ++NumParens;
-      } else if (Tok.is(tok::comma) && NumParens == 0 &&
-                 !(Tok.getFlags() & Token::IgnoredComma)) {
+      } else if (Tok.is(tok::comma)) {
         // In Microsoft-compatibility mode, single commas from nested macro
         // expansions should not be considered as argument separators. We test
-        // for this with the IgnoredComma token flag above.
-
-        // Comma ends this argument if there are more fixed arguments expected.
-        // However, if this is a variadic macro, and this is part of the
-        // variadic part, then the comma is just an argument token.
-        if (!isVariadic) break;
-        if (NumFixedArgsLeft > 1)
-          break;
+        // for this with the IgnoredComma token flag.
+        if (Tok.getFlags() & Token::IgnoredComma) {
+          // However, in MSVC's preprocessor, subsequent expansions do treat
+          // these commas as argument separators. This leads to a common
+          // workaround used in macros that need to work in both MSVC and
+          // compliant preprocessors. Therefore, the IgnoredComma flag can only
+          // apply once to any given token.
+          Tok.clearFlag(Token::IgnoredComma);
+        } else if (NumParens == 0) {
+          // Comma ends this argument if there are more fixed arguments
+          // expected. However, if this is a variadic macro, and this is part of
+          // the variadic part, then the comma is just an argument token.
+          if (!isVariadic)
+            break;
+          if (NumFixedArgsLeft > 1)
+            break;
+        }
       } else if (Tok.is(tok::comment) && !KeepMacroComments) {
         // If this is a comment token in the argument list and we're just in
         // -C mode (not -CC mode), discard the comment.
diff --git a/clang/test/Preprocessor/microsoft-ext.c b/clang/test/Preprocessor/microsoft-ext.c
--- a/clang/test/Preprocessor/microsoft-ext.c
+++ b/clang/test/Preprocessor/microsoft-ext.c
@@ -23,6 +23,19 @@
                 HAS_1_TEMPLATE_PARAMS(int, k),
                 AND_2_VALUE_PARAMS(p0, p1));
 
+// Regression test for PR43282; check that we match MSVC's failure to unpack
+// __VA_ARGS__ unless forwarded through another macro.
+#define THIRD_ARGUMENT(A, B, C, ...) C
+#define TEST(...) THIRD_ARGUMENT(__VA_ARGS__, 1, 2)
+#define COMBINE(...) __VA_ARGS__
+#define WRAPPED_TEST(...) COMBINE(THIRD_ARGUMENT(__VA_ARGS__, 1, 2))
+// Check that we match MSVC's failure to unpack __VA_ARGS__, unless forwarded
+// through another macro
+auto packed = TEST(,);
+auto unpacked = WRAPPED_TEST(,);
+// CHECK: auto packed = 2;
+// CHECK: auto unpacked = 1;
+
 // This tests compatibility with behaviour needed for type_traits in VS2012
 // Test based on _VARIADIC_EXPAND_0X macros in xstddef of VS2012
 #define _COMMA ,