diff --git a/llvm/lib/Target/X86/MCTargetDesc/X86AsmBackend.cpp b/llvm/lib/Target/X86/MCTargetDesc/X86AsmBackend.cpp
--- a/llvm/lib/Target/X86/MCTargetDesc/X86AsmBackend.cpp
+++ b/llvm/lib/Target/X86/MCTargetDesc/X86AsmBackend.cpp
@@ -332,6 +332,11 @@
   return (BaseReg == X86::RIP);
 }
 
+/// Check if the instruction is a prefix.
+static bool isPrefix(const MCInst &MI, const MCInstrInfo &MCII) {
+  return X86II::isPrefix(MCII.get(MI.getOpcode()).TSFlags);
+}
+
 /// Check if the instruction is valid as the first instruction in macro fusion.
 static bool isFirstMacroFusibleInst(const MCInst &Inst,
                                     const MCInstrInfo &MCII) {
@@ -505,6 +510,11 @@
     // instruction delay, inserting a nop would change behavior.
     return;
 
+  if (isPrefix(PrevInst, *MCII))
+    // If this instruction follows a prefix, inserting a nop would change
+    // semantic.
+    return;
+
   if (!isMacroFused(PrevInst, Inst))
     // Macro fusion doesn't happen indeed, clear the pending.
     PendingBoundaryAlign = nullptr;
diff --git a/llvm/test/MC/X86/align-branch-64-prefix.s b/llvm/test/MC/X86/align-branch-64-prefix.s
new file mode 100644
--- /dev/null
+++ b/llvm/test/MC/X86/align-branch-64-prefix.s
@@ -0,0 +1,76 @@
+  # RUN: llvm-mc -filetype=obj -triple x86_64-pc-linux-gnu --x86-align-branch-boundary=32 --x86-align-branch=jmp+call %s | llvm-objdump -d --no-show-raw-insn - | FileCheck %s
+
+  # Exercise cases where prefixes are specified for instructions to be aligned
+  # and thus can't add a nop in between without changing semantic.
+
+  .text
+
+  # CHECK: 1d:       int3
+  # CHECK: 1e:       jmp
+  # CHECK: 24:       int3
+  .p2align  5
+  .rept 30
+  int3
+  .endr
+  CS
+  jmp baz
+  int3
+
+  # CHECK: 5d:       int3
+  # CHECK: 5e:       jmp
+  # CHECK: 64:       int3
+  .p2align  5
+  .rept 30
+  int3
+  .endr
+  GS
+  jmp baz
+  int3
+
+  # CHECK: 9d:       int3
+  # CHECK: 9e:       call
+  # CHECK: a6:       int3
+  .p2align  5
+  .rept 30
+  int3
+  .endr
+  data16
+  call *___tls_get_addr@GOT(%ecx)
+  int3
+
+  # CHECK: de:       lock
+  # CHECK: df:       jmp
+  # CHECK: e4:       int3
+  .p2align  5
+  .rept 30
+  int3
+  .endr
+  lock
+  jmp baz
+  int3
+
+  # CHECK: 11d:       int3
+  # CHECK: 11e:       jmp
+  # CHECK: 124:       int3
+  .p2align  5
+  .rept 30
+  int3
+  .endr
+  rex64
+  jmp baz
+  int3
+
+  # CHECK: 15d:      int3
+  # CHECK: 15e:      {{.*}} jmp
+  # CHECK: 164:      int3
+  .p2align  5
+  .rept 30
+  int3
+  .endr
+  xacquire
+  jmp baz
+  int3
+
+  .section ".text.other"
+bar:
+  retq