We report the use of mechanical and pharmacologic catheter-directed thrombolysis in treating deep vein thrombosis with congenital absence of the inferior vena cava The patient presented with disabling bilateral lower extremity swelling and pain and was found to have extensive bilateral iliofemoral deep vein thromboses. Genetic testing revealed a factor V Leiden mutation. The patient underwent thrombolysis using a Possis (MEDRAD Inc, Warrendale, Pa) catheter and overnight infusion of tissue plasminogen activator. The patient tolerated the procedure well, with prompt return to daily activities. He remains free of symptoms at 3 years on oral anticoagulation, with a patent venous architecture.