The case of a 63-year-old woman with a Bjork-Shiley mitral valve prosthesis who developed acute thrombosis of mitral prosthesis and acute pulmonary edema is described. Full clinical success was achieved with medical therapy with tissue-type plasminogen activator. The dosage of drug was titrated by serial echo-Doppler examinations of prosthetic structures and functional area. A low-dose (60 mg over 1 hour) of tissue-type plasminogen activator was sufficient to obtain thrombus resolution. Embolic or hemorrhagic complications were absent. This is the first report of successful use of Doppler echocardiography titrated low-dose of tissue-type plasminogen activator for acute thrombosis of mitral prosthetic valve.