Conventional medical thought accepts the risks of nosocomial prosthetic valve endocarditis (PVE) to be between 0·7 and 1·4%, the incidence within several months after surgery. More careful actuarial analysis of recent series suggests the risk of nosocomial PVE is 1·4-3·0%, with cases occurring throughout the year after surgery. Methicillin-resistant coagulase-negative staphylococci are the predominant cause of nosocomial PVE and account for 60% of cases. Intraoperative contamination by Staphylococcus epidermidis of nosocomial origin has led to small epidemics of PVE. Aside from the fundamental elements of aseptic surgical technique, studies have failed to identify elements of intraoperative or postoperative care that might be modified to reduce the incidence of sporadic cases of nosocomial PVE. Prophylactic antibiotics have become an essential element in the effort to prevent PVE. Some recent studies have advocated using cefamandole or cefuroxime for prophylaxis; however, other studies have failed to find these agents more effective than cefazolin. The use of vancomycin for prophylaxis requires additional study. Intensive studies are needed to define elements of perioperative and postoperative care that can be modified to reduce the frequency of nosocomial PVE. © 1991.