Thrombosis is a serious complication of heart valve replacement. Diagnosis is often difficult with previously reported techniques, including precordial two-dimensional echocardiography, suffering from low sensitivity and specificity. Management is similarly difficult, with a 40% to 50% reported mortality rate in early surgical series. Three cases are presented in which thrombosis of a left-sided prosthetic valve (one aortic, three mitral) was diagnosed by means of transesophageal echocardiography. All three patients were treated with streptokinase and had clinical and echocardiographic resolution. In one patient, who had recurrent thrombosis and received a second course of streptokinase, the course was complicated by a massive embolic stroke and death. Another patient with a recurrence underwent successful valve replacement. Transesophageal echocardiography is ideal for the diagnosis and follow-up of patients with prosthetic valve thrombosis. Although effective, thrombolysis in this setting is associated with a high risk of thromboembolic phenomena and significant risk of death. Thrombolytic therapy may be considered in highly selected patients who have an unacceptable risk for reoperation.