Background: Carpal tunnel syndrome (CTS) is a sporadic event with compression of the median nerve (MN). Persistent median artery (PMA) thrombosis is an exceptionally rare cause of CTS. Case report: 38‐year‐old male presented with acute on subacute right wrist pain with positive Tinel's sign. An ultrasound and computed angiography study confirmed a PMA with thrombosis. The patient was treated with intravenous heparin then discharged home on enoxaparin and warfarin crossover. Discussion: PMA can lead to CTS by compression from the adjacent median nerve. Thrombosis of the PMA can also lead to CTS. Surgical intervention is needed in cases of severe CTS. Carpal tunnel release is usually successful. Excision of the PMA can risk vascular compromise of the digits. Ultrasound is excellent for detecting rare causes of CTS. Conclusion: Ultrasound examination for CTS should include search for PMA and associated anatomical variations.