From January 1963 until January 1974, 45 patients had prosthetic valve endocarditis. Symptoms of prosthetic valve endocarditis developed within 2 months after operation (early onset) in 16 patients (36%) and more than 2 months after operation (late onset) in 29 patients (64%). Overall mortality among the 45 patients was 56% (88% among those with early onset and 40% among those with late onset). Medical therapy alone was curative in 60% of the surviving patients. Combined medical and surgical therapy was curative in 40% of the survivors. The most frequent isolates in the early-onset group were Staphylococcus aureus (44%) and Gram-negative bacilli (38%); associated mortality was 86% and 83%, respectively. The most frequent isolates in the late-onset group were viridans streptococci (41%) and Gram-negative bacilli (31%); the mortality was 25% and 22% respectively. Suggestions are offered for operative antimicrobial prophylaxis and for medical and surgical treatment of prosthetic valve endocarditis. Prompt surgical replacement of an infected prosthesis is necessary when medical therapy fails.