diff --git a/llvm/lib/Transforms/InstCombine/InstCombineCalls.cpp b/llvm/lib/Transforms/InstCombine/InstCombineCalls.cpp
--- a/llvm/lib/Transforms/InstCombine/InstCombineCalls.cpp
+++ b/llvm/lib/Transforms/InstCombine/InstCombineCalls.cpp
@@ -1787,8 +1787,11 @@
 /// instructions. For normal calls, it allows visitCallBase to do the heavy
 /// lifting.
 Instruction *InstCombiner::visitCallInst(CallInst &CI) {
-  if (Value *V = SimplifyCall(&CI, SQ.getWithInstruction(&CI)))
-    return replaceInstUsesWith(CI, V);
+  // Don't try to simplify calls without uses. It will not do anything useful,
+  // but will result in the following folds being skipped.
+  if (!CI.use_empty())
+    if (Value *V = SimplifyCall(&CI, SQ.getWithInstruction(&CI)))
+      return replaceInstUsesWith(CI, V);
 
   if (isFreeCall(&CI, &TLI))
     return visitFree(CI);
diff --git a/llvm/test/Transforms/InstCombine/pr44245.ll b/llvm/test/Transforms/InstCombine/pr44245.ll
--- a/llvm/test/Transforms/InstCombine/pr44245.ll
+++ b/llvm/test/Transforms/InstCombine/pr44245.ll
@@ -59,7 +59,7 @@
 ; CHECK-NEXT:    br label [[BB47]]
 ; CHECK:       bb152:
 ; CHECK-NEXT:    [[TMP1848]] = load i8*, i8** inttoptr (i64 16 to i8**), align 16
-; CHECK-NEXT:    call void undef()
+; CHECK-NEXT:    store i1 true, i1* undef, align 1
 ; CHECK-NEXT:    br label [[BB150]]
 ;
 bb16:                                             ; preds = %bb