OBJECTIVE We analyzed the short- and long-term results for patients undergoing thrombolysis of occluded infrainguinal bypass grafts at our institution over a 62-month period. METHODS Thirty-one patients with 40 episodes of graft thrombosis in 33 grafts managed by thrombolysis were retrospectively reviewed. The effects of graft age, material, and anatomy, symptoms, treatment, anticoagulation, and occlusion duration were evaluated for impact on patency after thrombolysis. Dose and duration of therapy with use of the technique of pulse-spray thrombolysis was assessed. RESULTS Thrombolysis successfully reestablished patency in 92% of grafts treated. Mean lysis time and urokinase dose were 118 minutes and 607,000 units, respectively. Responsible lesions were identified and treated by angioplasty or surgery in 35 of 37 cases. The patency rate after thrombolysis was 28% at 30 months, and the secondary patency rate was 46% at 18 months. Duration of occlusion, symptoms, treatment, graft anatomy, and prior graft revision did not impact on patency. Mean secondary patency was 21.5 months in grafts in place over 1 year and 7.0 months in grafts in place for less than 1 year. Mean secondary patency was 23.8 months in polytetrafluoroethylene grafts and 8.4 months in vein grafts. The limb salvage rate was 84% at 30 months, and the patient survival rate was 84% at 42 months. CONCLUSIONS Pulse-spray thrombolysis is effective in rapidly recanalizing thrombosed infrainguinal grafts. Grafts failing in the first year after placement should generally be replaced, reserving thrombolysis and revision for grafts greater than 1 year old. Vein grafts tolerate thrombosis less well than synthetic conduits and have decreased long-term patency.