BACKGROUND AND AIM OF THE STUDY: Emergency valve replacement has long been the treatment of choice in left-sided prosthetic valve thrombosis (PVT) for critically ill patients in NYHA classes III-IV. Thrombolytic therapy is recommended for NYHA class I/II patients with a small thrombotic burden. METHODS: The results of thrombolytic therapy to treat left-sided PVT (eight mitral, three aortic) with streptokinase (STK) in critically ill NYHA class III/IV patients were analyzed, where surgery was either refused due to financial constraints or by the surgical team. Results were assessed clinically, using fluoroscopy and transthoracic and transesophageal echocardiography. RESULTS: Mechanical bileaflet prosthetic valves (eight mitral, four aortic) were implanted between two and 10 years previously in 11 patients (four females, seven males; age range: 32-54 years). One patient had diabetes and had undergone prior percutaneous coronary intervention with drug-eluting stent implantation to the ostial left main artery. All had cardiomegaly with ejection fraction 24-63% and an increased mean gradient across the immobile prosthetic valve. Patients presented in a hemodynamically unstable state with pulmonary edema and/or hypotensive shock. The International Normalized Ratio was <2.5 in nine patients. Eight patients with mitral valve thrombosis responded to thrombolytic therapy and survived, with complete resolution of thrombus and return of full mobility of leaflets and resolution of valve gradients. To date, all responders have survived (up to five years) without any recurrence of re-thrombosis (PVT). CONCLUSION: Intravenous STK may be life-saving in critically ill NYHA class III/IV patients with left-sided PVT. Thrombolytic therapy is much cheaper and easier to administer than surgical replacement of the thrombosed prosthetic valve.