diff --git a/qiskit/transpiler/passes/synthesis/unitary_synthesis.py b/qiskit/transpiler/passes/synthesis/unitary_synthesis.py
index 139add90ee56..0bef46e62523 100644
--- a/qiskit/transpiler/passes/synthesis/unitary_synthesis.py
+++ b/qiskit/transpiler/passes/synthesis/unitary_synthesis.py
@@ -25,6 +25,7 @@
 from qiskit.quantum_info.synthesis import one_qubit_decompose
 from qiskit.quantum_info.synthesis.xx_decompose import XXDecomposer
 from qiskit.quantum_info.synthesis.two_qubit_decompose import TwoQubitBasisDecomposer
+from qiskit.circuit import ControlFlowOp
 from qiskit.circuit.parameter import Parameter
 from qiskit.circuit.library.standard_gates import (
     iSwapGate,
@@ -35,6 +36,7 @@
     ECRGate,
 )
 from qiskit.transpiler.passes.synthesis import plugin
+from qiskit.transpiler.passes.utils import control_flow
 from qiskit.providers.models import BackendProperties
 
 
@@ -258,7 +260,6 @@ def run(self, dag: DAGCircuit) -> DAGCircuit:
             plugin_method = DefaultUnitarySynthesis()
         plugin_kwargs = {"config": self._plugin_config}
         _gate_lengths = _gate_errors = None
-        dag_bit_indices = {}
 
         if self.method == "default":
             # If the method is the default, we only need to evaluate one set of keyword arguments.
@@ -278,8 +279,6 @@ def run(self, dag: DAGCircuit) -> DAGCircuit:
         for method, kwargs in method_list:
             if method.supports_basis_gates:
                 kwargs["basis_gates"] = self._basis_gates
-            if method.supports_coupling_map:
-                dag_bit_indices = dag_bit_indices or {bit: i for i, bit in enumerate(dag.qubits)}
             if method.supports_natural_direction:
                 kwargs["natural_direction"] = self._natural_direction
             if method.supports_pulse_optimize:
@@ -306,6 +305,29 @@ def run(self, dag: DAGCircuit) -> DAGCircuit:
         if self.method == "default":
             # pylint: disable=attribute-defined-outside-init
             plugin_method._approximation_degree = self._approximation_degree
+        return self._run_main_loop(
+            dag, plugin_method, plugin_kwargs, default_method, default_kwargs
+        )
+
+    def _run_main_loop(self, dag, plugin_method, plugin_kwargs, default_method, default_kwargs):
+        """Inner loop for the optimizer, after all DAG-idependent set-up has been completed."""
+
+        def _recurse(dag):
+            # This isn't quite a trivially recursive call because we need to close over the
+            # arguments to the function.  The loop is sufficiently long that it's cleaner to do it
+            # in a separate method rather than define a helper closure within `self.run`.
+            return self._run_main_loop(
+                dag, plugin_method, plugin_kwargs, default_method, default_kwargs
+            )
+
+        for node in dag.op_nodes(ControlFlowOp):
+            node.op = control_flow.map_blocks(_recurse, node.op)
+
+        dag_bit_indices = (
+            {bit: i for i, bit in enumerate(dag.qubits)}
+            if plugin_method.supports_coupling_map or default_method.supports_coupling_map
+            else {}
+        )
 
         for node in dag.named_nodes(*self._synth_gates):
             if self._min_qubits is not None and len(node.qargs) < self._min_qubits:
diff --git a/test/python/transpiler/test_unitary_synthesis.py b/test/python/transpiler/test_unitary_synthesis.py
index 253ec2939ee7..93365a13fe35 100644
--- a/test/python/transpiler/test_unitary_synthesis.py
+++ b/test/python/transpiler/test_unitary_synthesis.py
@@ -26,9 +26,9 @@
 from qiskit.test import QiskitTestCase
 from qiskit.providers.fake_provider import FakeVigo, FakeMumbaiFractionalCX
 from qiskit.providers.fake_provider.fake_backend_v2 import FakeBackendV2, FakeBackend5QV2
-from qiskit.circuit import QuantumCircuit, QuantumRegister
+from qiskit.circuit import QuantumCircuit, QuantumRegister, ClassicalRegister
 from qiskit.circuit.library import QuantumVolume
-from qiskit.converters import circuit_to_dag
+from qiskit.converters import circuit_to_dag, dag_to_circuit
 from qiskit.transpiler.passes import UnitarySynthesis
 from qiskit.quantum_info.operators import Operator
 from qiskit.quantum_info.random import random_unitary
@@ -724,6 +724,48 @@ def test_reverse_direction(self, opt_level):
         for instr in tqc.get_instructions("ecr"):
             self.assertEqual((0, 1), (tqc_index[instr.qubits[0]], tqc_index[instr.qubits[1]]))
 
+    def test_if_simple(self):
+        """Test a simple if statement."""
+        basis_gates = {"u", "cx"}
+        qr = QuantumRegister(2)
+        cr = ClassicalRegister(2)
+
+        qc_uni = QuantumCircuit(2)
+        qc_uni.h(0)
+        qc_uni.cx(0, 1)
+        qc_uni_mat = Operator(qc_uni)
+
+        qc_true_body = QuantumCircuit(2)
+        qc_true_body.unitary(qc_uni_mat, [0, 1])
+
+        qc = QuantumCircuit(qr, cr)
+        qc.if_test((cr, 1), qc_true_body, [0, 1], [0, 1])
+        dag = circuit_to_dag(qc)
+        cdag = UnitarySynthesis(basis_gates=basis_gates).run(dag)
+        cqc = dag_to_circuit(cdag)
+        cbody = cqc.data[0].operation.params[0]
+        self.assertEqual(cbody.count_ops().keys(), basis_gates)
+        self.assertEqual(qc_uni_mat, Operator(cbody))
+
+    def test_nested_control_flow(self):
+        """Test unrolling nested control flow blocks."""
+        qr = QuantumRegister(2)
+        cr = ClassicalRegister(1)
+        qc_uni1 = QuantumCircuit(2)
+        qc_uni1.swap(0, 1)
+        qc_uni1_mat = Operator(qc_uni1)
+
+        qc = QuantumCircuit(qr, cr)
+        with qc.for_loop(range(3)):
+            with qc.while_loop((cr, 0)):
+                qc.unitary(qc_uni1_mat, [0, 1])
+        dag = circuit_to_dag(qc)
+        cdag = UnitarySynthesis(basis_gates=["u", "cx"]).run(dag)
+        cqc = dag_to_circuit(cdag)
+        cbody = cqc.data[0].operation.params[2].data[0].operation.params[0]
+        self.assertEqual(cbody.count_ops().keys(), {"u", "cx"})
+        self.assertEqual(qc_uni1_mat, Operator(cbody))
+
 
 if __name__ == "__main__":
     unittest.main()