Antiphospholipid antibody syndrome (APAS) commonly presents with cutaneous infarctions mimicking thromboembolic vaso-occlusive disease. Systemic anticoagulation is the standard of care for this disorder, but treatment failures can occur. The authors report the first successful treatment of cutaneous infarctions due to APAS with low-dose, intravenous tissue plasminogen activator (rTPA) in a patient who failed to improve with high-dose anticoagulation. Wound healing was associated with a marked improvement in blood flow as assessed by scanning laser Doppler. The authors recommend that patients presenting with cutaneous infarctions in the absence of atherosclerosis be evaluated for APAS, and that fibrinolytic therapy be considered if cutaneous infarction persists despite anticoagulant therapy.