Prosthetic heart valve dysfunction is an acquired condition that carries a significant risk of emergency surgery. However, the long-term natural history of the condition is not well understood. Between 1974 and 2006, 1535 isolated mitral valve replacements were performed at our hospital (in-hospital mortality 5%). In total, 369 patients needed a second operation (in-hospital mortality 8.1%), while 80 (age 59.8+/-11.4 years) needed a third. The reasons for the third intervention were structural deterioration (67.5%), paravalvular leak (20%) and endocarditis (6.3%). Some 15 patients died in hospital (18.8%). After a mean follow-up period of 17.8 years, 21 patients needed another intervention (i.e., a fourth intervention). The actuarial reoperation-free rate at 20 years was 40.1+/-13.8%. The late mortality rate was 58.5% (18-year survival rate 15.4+/-5.4%). Indications for repeat mitral valve replacement must be judged on an individual basis given the high risk associated with surgery.