This prospective study evaluated the clinical performance of a novel stentless quadrileaflet bovine pericardial mitral valve implanted at one center since December 1996. After giving informed consent, patients were included in the study if they required isolated mitral valve replacement. All underwent comprehensive clinical evaluation, as well as transthoracic M-mode, two-dimensional and Doppler (pulsed, continuous, and color) echocardiography preoperatively and postoperatively at 1 month, 3 months, and annually thereafter. Mitral valve area was derived by planimetry, the pressure half-time method, and the continuity equation. The degree of mitral regurgitation was semi-quantitated using color Doppler. In all 38 patients with rheumatic valvular heart disease (mean age 35+/-13 years) were monitored for 13.8+/-7.5 months (range, 1 to 29 months). All but three patients are alive and symptomatically improved (functional New York Heart Association class I or II). One valve was explanted because of early prosthetic valve endocarditis. There were no episodes of thromboembolism or anticoagulation-related hemorrhage. Left ventricular function was maintained with increased cardiac output and low transmitral pressure gradients. The mitral valve area was larger when measured by pressure half-time and planimetry than by the continuity equation (P<.05). In an independent clinical evaluation of a subset of 30 patients, mitral stenosis was considered absent in 33%, mild in 30%, mild to moderate in 26%, and moderate in 10% of cases. No or less than or equal to mild mitral regurgitation was noted in the majority of patients postoperatively, both clinically and echocardiographically. We are encouraged by the clinical performance of the quadrileaflet mitral valve and with patient outcome. Long-term follow-up data are needed to assess durability.