BACKGROUND We recently reported that valve prosthesis-patient mismatch (PPM) is associated with persisting pulmonary hypertension after mitral valve replacement. Thus, the objective of this study was to evaluate the impact of PPM on mortality in patients undergoing mitral valve replacement. RESULTS The indexed valve effective orifice area was estimated for each type and size of prosthesis being implanted in 929 consecutive patients and used to define PPM as not clinically significant if > 1.2 cm2/m2, as moderate if > 0.9 and < or = 1.2 cm2/m2, and as severe if < or = 0.9 cm2/m2. Moderate PPM was present in 69% of patients; severe PPM was seen in 9%. For patients with severe PPM, 6-year survival (74+/-5%) and 12-year survival (63+/-7%) were significantly less than for patients with moderate PPM (84+/-1% and 76+/-2%; P=0.027) or nonsignificant PPM (90+/-2% and 82+/-4%; P=0.002). On multivariate analysis, severe PPM was associated with higher mortality (hazard ratio, 3.2; 95% confidence interval, 1.5 to 6.8; P=0.003). CONCLUSIONS Severe PPM is an independent predictor of mortality after mitral valve replacement. As opposed to other independent risk factors, PPM may be avoided or its severity may be reduced with the use of a prospective strategy at the time of operation. For patients identified as being at risk for severe PPM, every effort should be made to implant a prosthesis with a larger effective orifice area.