Eight dogs with naturally occurring severe mitral regurgitation underwent mitral valve replacement with a mechanical valve prosthesis during cardiopulmonary bypass. Dogs received warfarin orally after surgery to maintain a prothrombin time-based international normalized ratio from 2.5 to 3.5. Seven dogs survived surgery. Left ventricular diastolic volume index decreased significantly from 206 +/- 91 mL/m2 before surgery to 121 +/- 47 mL/m2 after surgery. Left atrium-to-aorta ratio decreased significantly from 2.66 +/- 0.4 before surgery to 1.73 +/- 0.65 after surgery. Left ventricular systolic volume index was not significantly different after surgery (56 +/- 36 mL/m2), compared with before surgery (40 +/- 32 mL/m2). Median survival after surgery was 4.5 months (range, 0.75 months to 5.25 years). Six dogs died of confirmed or suspected thrombosis of the valve prosthesis. Dogs with severe mitral regurgitation tolerated mitral valve replacement well, but a high incidence of prosthetic valve thrombosis limited long-term outcome.