Prosthetic valve thrombosis can determine different degrees of valvular insufficiency or obstruction, with a potentially fatal course. The current literature has not established whether the best treatment is thrombolysis or surgery (thrombectomy or valvular replacement). However, both treatments expose the patient to the risk of serious sequelae or death. Here we describe a case of acute thrombosis in a prosthetic mitral valve. At presentation, the patient was in pulmonary edema and had a low cardiac output. She was treated with recombinant tissue-type plasminogen activator infusion (rt-PA 100 mg in 2 hours). Both clinically as well as echocardiographically, we observed a quick regression of the obstruction, but after the treatment, the patient developed an ischemic stroke with aphasia and hemiplegia. The authors conclude that thrombolysis is a highly effective treatment in resolving prosthetic thrombosis. However, because it carries a significant risk of embolization, it should be limited to patients with hemodynamic deterioration in whom surgery could also entail a significant risk of death.