Randomized clinical trials have defined anticoagulation with unfractionated or low molecular weight heparin followed by warfarin as standard therapy for acute deep venous thrombosis (DVT). Such treatment is highly effective in preventing recurrent venous thromboembolism, but provides imperfect protection against development of the postthrombotic syndrome. By restoring venous patency and preserving valvular function, catheter-directed thrombolytic therapy potentially affords an improved long-term outcome in selected patients with DVT. A national venous registry, compiling data from 63 participating centers, was established to collect data regarding the technical details of the procedure and early outcome. Data from the registry have established the optimal technical approach and patient population. An antegrade catheter-directed approach using urokinase in patients with acute iliofemoral DVT of less than 10 days duration and no prior history of DVT may achieve complete lysis in 65% of patients. Analysis of the clinical outcome is pending, but early results suggest improved valve function and fewer symptoms at 1 year in patients with complete thrombolysis. These promising data should serve as the basis for future randomized trials of catheterdirected thrombolysis for the treatment of acute DVT.