Pregnancy and the postpartum period are generally considered as contraindications for thrombolysis. We evaluate in this report the safety and effectiveness of using ultrasound-accelerated catheter-directed thrombolysis (UACDT) in treating three symptomatic postpartum deep vein thrombosis (DVT). UACDT was performed using a recombinant human tissue plasminogen activator (alteplase) which was delivered using the EKOS EkoSonic® system. Postprocedure venography was repeated after treatment which include stenting if stenosis was present. The treatment was successful in all three cases of iliofemoral DVT and symptom relief was achieved in all cases. Minor bleeding at the catheter insertion site in one patient was observed but none of the patients suffered from major bleeding or symptomatic pulmonary embolism. UACDT is a safe and effective treatment for restoration of the venous flow in patients with postpartum iliofemoral DVT. Residual venous obstruction should be treated by angioplasty and stent insertion to avoid early re-thrombosis.