Patients undergoing repeat heart valve operations are a diverse population. We assessed risk factors for operative mortality in patients undergoing a first heart valve reoperation. A retrospective review of hospital records was performed for 671 patients who underwent first repeat heart valve operations between 1969 and 1998. Univariable and multivariable analyses were performed. Operative mortality was 8.6%. Mortality fell each decade to 4.8% in the most recent period (adjusted chi(2) for linear trend P <.0005). Mortality increased from 3.0% for reoperation for a failed repair or reoperation at a new valve site to 10.6% for prosthetic valve dysfunction or periprosthetic leak and to 29.4% for endocarditis or valve thrombosis. Concomitant coronary artery bypass grafting was associated with a mortality of 15.4% compared with 8.2% when it was not required. Mortality for aortic valve replacement was 6.4%, mitral valve replacement 7.4%, aortic and mitral valve replacement 11.5%, tricuspid valve replacement 25.6%, periprosthetic leak repair 9.1%, and isolated valve repair 2.2%. Among 336 patients requiring replacement of prosthetic valves, mortality was 26.1% for replacement of a mechanical valve compared with 8.6% for replacement of a tissue valve (P <.0005). Multivariable analyses identified year of reoperation, age, coronary artery bypass grafting, indication, and replacement of a mechanical valve rather than a tissue valve as significant explanatory variables for operative mortality. Heart valve reoperations can be performed with an acceptable operative mortality. However, we have identified several categories of patients in whom reoperation carries an increased risk.