The diagnosis, therapy, and complications of prosthetic valve endocarditis (PVE) in 48 patients seen between 1962 and 1978 are reviewed. Staphylococcus epidermidis and diphtheroids were the most common causes of both early and late PVE. These microorganisms were frequently resistant to the penicillins and cephalosporins but were uniformly sensitive to vancomycin. The mortality rate in this series was 69%, with 20% of the deaths attributed to central nervous system emboli and the remainder to cardiac causes. The mortality rate exceeded 75% in patients with any of the following findings: aortic valve infection, nonstreptococcal infecting microorganism, new or increased regurgitant murmurs, or significant congestive heart failure (CHF). The mortality rate was lowest in streptococcal PVE (29%) and in mitral valve PVE (49%). The unacceptably high mortality rate suggests that early replacement of infected prostheses should be considered in all patients except those with uncomplicated streptoccal or mitral valve PVE.