Thrombosis of left-sided prosthetic valves is an uncommon yet potentially serious complication. Thrombolytic therapy has been proposed as an alternative to surgical methods in treating this condition. We sought to determine from a review of the literature what outcomes may be expected subsequent to thrombolytic administration and what groups may be at risk or benefit from this approach. We searched for studies including two or more patients treated with thrombolytic agents. Ten studies were reviewed. We describe and include two patients with valve thrombosis treated at our institution. A total of 182 episodes of prosthetic valve thrombosis in 162 patients were examined. Clinical success was achieved in 72.0% of cases and there was a mortality risk of 9.9%. Clinical success from thrombolysis was significantly related to the degree of heart failure at presentation and aortic valve position. Clinical success was not related to the duration of symptoms, time from valve replacement to obstruction, or valve type. Rethrombosis of successfully treated valve occurred subsequently in 19.5% of cases. Repeated thrombolytic administration in these patients was associated with similar rates of success as those treated for their initial episode of prosthetic valve thrombosis. Candidates for thrombolytic therapy include patients with obstructive valve thrombosis with or without congestive heart failure who are hemodynamically stable. Duration of time since valve replacement or symptom onset does not limit successful outcome. Close observation and aggressive maintenance of anticoagulation after therapy is suggested.