Objective: To evaluate nonsurgical alternatives in reopening chronically occluded aortic bifurcation. Design: Uncontrolled randomized study. Setting: University-affiliated referral center for vascular diseases. Patients: Twenty-five of 39 consecutive patients with chronic aortoiliac disease including a totally occluded aortic bifurcation were found to be acceptable candidates for an aortobifemoral prosthetic graft. Intervention: Patients were randomly assigned to receive either streptokinase or urokinase or recombinant tissue-type plasminogen activator (rt-PA). In cases of successful thrombolysis and residual obstructions, subsequent balloon angioplasty was attempted. Prosthetic bypass grafting was done if thrombolytic treatment and balloon angioplasty failed. Results: Complete lysis was achieved in 5 of 25 patients (20%). In 10 (40%) patients, lysis showed residual obstructions, which were reopened mechanically in 8 patients; 2 patients had extra-anatomical bypass grafts. Ten patients (40%) without thrombolysis had surgical aortobifemoral bypass grafts. Overall, recanalization and clinical improvement were achieved in 13 of 25 patients (52%) by thrombolytic therapy and subsequent balloon angioplasty. The recanalization rate did not differ among the different thrombolytic drugs. However, rt-PA therapy resulted in reopening after 4 days of treatment; streptokinase, after 6 days; and urokinase, after 9 days (P < 0.005). No major complications or deaths occurred. Conclusion: Thrombolytic treatment followed by balloon angioplasty may help avoid the need for aortobifemoral prosthetic bypass grafting in more than 50% of patients with chronic aortoiliac disease.