diff --git a/cranelift/filetests/regalloc/multi-constraints.cton b/cranelift/filetests/regalloc/multi-constraints.cton
index 80dc8f0658..ecb3aa8bad 100644
--- a/cranelift/filetests/regalloc/multi-constraints.cton
+++ b/cranelift/filetests/regalloc/multi-constraints.cton
@@ -27,3 +27,26 @@ ebb0(v0: i64, v1: i64, v2: i64, v3: i64):
 ebb1:
     return v4
 }
+
+; Found by the Binaryen fuzzer in PR218.
+;
+; This is a similar situation involving combined constraints on the ushr instruction:
+;
+; - The %rcx register is already in use by a globally live value.
+; - The ushr x, x result is also a globally live value.
+;
+; Since the ushr x, x result is forced to be placed in %rcx, we must set the replace_global_defines
+; flag so it can be reassigned to a different global register.
+function %pr218(i64 [%rdi], i64 [%rsi], i64 [%rdx], i64 [%rcx]) -> i64 [%rax] {
+ebb0(v0: i64, v1: i64, v2: i64, v3: i64):
+    ; check: regmove $v3, %rcx ->
+    v4 = ushr v0, v0
+    ; check: $v4 = copy
+    jump ebb1
+
+ebb1:
+    ; v3 is globally live in %rcx.
+    ; v4 is also globally live. Needs to be assigned something else for the trip across the CFG edge.
+    v5 = iadd v3, v4
+    return v5
+}
diff --git a/lib/cretonne/src/regalloc/coloring.rs b/lib/cretonne/src/regalloc/coloring.rs
index 18d141eb75..74d80e1832 100644
--- a/lib/cretonne/src/regalloc/coloring.rs
+++ b/lib/cretonne/src/regalloc/coloring.rs
@@ -411,7 +411,13 @@ impl<'a> Context<'a> {
                 &regs.global,
             );
         }
-        self.program_output_constraints(inst, constraints.outs, defs);
+        self.program_output_constraints(
+            inst,
+            constraints.outs,
+            defs,
+            &mut replace_global_defines,
+            &regs.global,
+        );
 
         // Finally, we've fully programmed the constraint solver.
         // We expect a quick solution in most cases.
@@ -794,6 +800,8 @@ impl<'a> Context<'a> {
         inst: Inst,
         constraints: &[OperandConstraint],
         defs: &[LiveValue],
+        replace_global_defines: &mut bool,
+        global_regs: &AllocatableSet,
     ) {
         for (op, lv) in constraints.iter().zip(defs) {
             match op.kind {
@@ -807,12 +815,26 @@ impl<'a> Context<'a> {
                     // Find the input operand we're tied to.
                     // The solver doesn't care about the output value.
                     let arg = self.cur.func.dfg.inst_args(inst)[num as usize];
-                    self.solver.add_tied_input(
+                    if let Some(reg) = self.solver.add_tied_input(
                         arg,
                         op.regclass,
                         self.divert.reg(arg, &self.cur.func.locations),
                         !lv.is_local,
-                    );
+                    )
+                    {
+                        // The value we're tied to has been assigned to a fixed register.
+                        // We need to make sure that fixed output register is compatible with the
+                        // global register set.
+                        if !lv.is_local && !global_regs.is_avail(op.regclass, reg) {
+                            dbg!(
+                                "Tied output {} in {}:{} is not available in global regs",
+                                lv.value,
+                                op.regclass,
+                                self.reginfo.display_regunit(reg)
+                            );
+                            *replace_global_defines = true;
+                        }
+                    }
                 }
             }
         }
diff --git a/lib/cretonne/src/regalloc/solver.rs b/lib/cretonne/src/regalloc/solver.rs
index c7b884ce43..b5d5aa661b 100644
--- a/lib/cretonne/src/regalloc/solver.rs
+++ b/lib/cretonne/src/regalloc/solver.rs
@@ -760,14 +760,22 @@ impl Solver {
     ///
     /// The output value that must have the same register as the input value is not recorded in the
     /// solver.
-    pub fn add_tied_input(&mut self, value: Value, rc: RegClass, reg: RegUnit, is_global: bool) {
+    ///
+    /// If the value has already been assigned to a fixed register, return that.
+    pub fn add_tied_input(
+        &mut self,
+        value: Value,
+        rc: RegClass,
+        reg: RegUnit,
+        is_global: bool,
+    ) -> Option<RegUnit> {
         debug_assert!(self.inputs_done);
 
         // If a fixed assignment is tied, the `to` register is not available on the output side.
         if let Some(a) = self.assignments.get(value) {
             debug_assert_eq!(a.from, reg);
             self.regs_out.take(a.rc, a.to);
-            return;
+            return Some(a.to);
         }
 
         // Check if a variable was created.
@@ -775,7 +783,7 @@ impl Solver {
             assert!(v.is_input);
             v.is_output = true;
             v.is_global = is_global;
-            return;
+            return None;
         }
 
         // No variable exists for `value` because its constraints are already satisfied.
@@ -790,6 +798,8 @@ impl Solver {
         } else {
             self.regs_out.take(rc, reg);
         }
+
+        None
     }
 
     /// Add a fixed output assignment.