From 1975 through 1992, we reoperated on 146 patients for the treatment of prosthetic valve endocarditis. Prosthetic valve endocarditis was considered to be early (< 1 year after operation) in 46 cases and active in 103 cases. The extent of the infection was prosthesis only in 66 patients, anulus in 46, and cardiac invasion in 34. Surgical techniques evolved in the direction of increasingly radical débridement of infected tissue and reconstruction with biologic materials. All patients were treated with prolonged postoperative antibiotic therapy. There were 19 (13%) in-hospital deaths. Univariate analyses demonstrated trends toward increasing risk for patients with active endocarditis and extension of infection beyond the prosthesis; however, the only variables with a significant (p < 0.05) association with increased in-hospital mortality confirmed with multivariate testing were impaired left ventricular function, preoperative heart block, coronary artery disease, and culture of organisms from the surgical specimen. During the study period, mortality decreased from 20% (1975 to 1984) to 10% (1984 to 1992). For hospital survivors the mean length of stay was 25 days. Follow-up (mean interval 62 months) documented a late survival of 82% at 5 postoperative years and 60% at 10 years. Older age was the only factor associated (p = 0.006) with late death. Nineteen patients needed at least one further operation; reoperation-free survival was 75% at 5 and 50% at 10 postoperative years. Fever in the immediate preoperative period was the only factor associated with decreased late reoperation-free survival (p = 0.032). Prosthetic valve endocarditis remains a serious complication of valve replacement, but the in-hospital mortality of reoperations for prosthetic valve endocarditis has declined. With extensive débridement of infected tissue and postoperative antibiotic therapy, the extent and activity of prosthetic valve endocarditis does not appear to have a major impact on late outcome, and the majority of patients with this complication survive for 10 years after the operation.