diff --git a/llvm/lib/CodeGen/AsmPrinter/AsmPrinter.cpp b/llvm/lib/CodeGen/AsmPrinter/AsmPrinter.cpp
--- a/llvm/lib/CodeGen/AsmPrinter/AsmPrinter.cpp
+++ b/llvm/lib/CodeGen/AsmPrinter/AsmPrinter.cpp
@@ -247,6 +247,11 @@
   if (DD) {
     assert(OutStreamer->hasRawTextSupport() &&
            "Expected assembly output mode.");
+    // This is NVPTX specific and it's unclear why.
+    // PR51079: If we have code without debug information we need to give up.
+    DISubprogram *MFSP = MF.getFunction().getSubprogram();
+    if (!MFSP)
+      return;
     (void)DD->emitInitialLocDirective(MF, /*CUID=*/0);
   }
 }
diff --git a/llvm/test/DebugInfo/NVPTX/crash-missing-DISubprogram.ll b/llvm/test/DebugInfo/NVPTX/crash-missing-DISubprogram.ll
new file mode 100644
--- /dev/null
+++ b/llvm/test/DebugInfo/NVPTX/crash-missing-DISubprogram.ll
@@ -0,0 +1,26 @@
+target triple = "nvptx64-nvidia-cuda"
+
+define weak i32 @test(i32* %a) {
+entry:
+  %r = load i32, i32* %a, !dbg !10
+  ret i32 %r
+}
+
+!llvm.module.flags = !{!0, !1, !2, !3, !4, !5, !6, !7}
+!llvm.dbg.cu = !{!8}
+
+!0 = !{i32 2, !"SDK Version", [2 x i32] [i32 11, i32 4]}
+!1 = !{i32 7, !"Dwarf Version", i32 2}
+!2 = !{i32 2, !"Debug Info Version", i32 3}
+!3 = !{i32 1, !"wchar_size", i32 4}
+!4 = !{i32 7, !"openmp", i32 50}
+!5 = !{i32 7, !"openmp-device", i32 50}
+!6 = !{i32 7, !"PIC Level", i32 2}
+!7 = !{i32 7, !"frame-pointer", i32 2}
+!8 = distinct !DICompileUnit(language: DW_LANG_C_plus_plus_14, file: !9, producer: "clang version 14.0.0 (https://github.com/llvm/llvm-project.git a0262043bb87fdef68c817722de320a5dd9eb9c9)", isOptimized: true, runtimeVersion: 0, emissionKind: DebugDirectivesOnly, splitDebugInlining: false, nameTableKind: None)
+!9 = !DIFile(filename: "test_omp_complex_reduction.cpp", directory: "/gpfs/jlse-fs0/users/jdoerfert/build/miniqmc-trunk/src/Platforms/tests/OMPTarget")
+!10 = !DILocation(line: 69, column: 18, scope: !11)
+!11 = distinct !DISubprogram(name: "__omp_outlined__1", scope: !12, file: !12, line: 68, type: !13, scopeLine: 68, flags: DIFlagPrototyped, spFlags: DISPFlagLocalToUnit | DISPFlagDefinition | DISPFlagOptimized, unit: !8, retainedNodes: !14)
+!12 = !DIFile(filename: "projects/benchmarks/miniqmc/src/Platforms/tests/OMPTarget/test_omp_complex_reduction.cpp", directory: "/gpfs/jlse-fs0/users/jdoerfert")
+!13 = !DISubroutineType(types: !14)
+!14 = !{}