The efficacy of thrombolytic agents in the management of peripheral arterial disease remains unclear. We reviewed our experience with 64 consecutive episodes of limb-threatening graft or native vessel occlusions. The overall success rate was 59%, with a major complication/mortality rate of 28%. Thrombolytic therapy in patients with occluded vascular grafts required identification of a causative lesion and subsequent adjunctive management with percutaneous transluminal angioplasty or surgery for sustained patency (64%). In contrast, approximately 70% of native vessel occlusions maintained patency whether a causative lesion was identified and corrected or not. Patients who failed thrombolytic therapy had a worse prognosis overall, with 38% undergoing primary amputation, although patients with reconstructable occlusions still had a 64% salvage rate at six months. The review demonstrated that thrombolytic therapy continues to be a useful adjunct in treating the patient with peripheral vascular occlusion, although a significant risk of major complications persists. Patients with graft occlusions successfully treated with thrombolysis require correction of any precipitating lesions for long-term limb salvage, while careful management of patients failing thrombolysis can still achieve significant limb salvage in selected cases.