Sixteen patients with coagulase-negative staphylococcal endocarditis were treated at the University of Minnesota Hospitals between January 1970 and September 1977. In six patients, endocarditis developed after prosthetic valve surgery; among the other ten patients (the medical group), eight had known antecedent valvular disease. The skin was thought to be the source of infection in eight patients, suggesting that prompt treatment of skin infections and avoidance of injections in patients with valvular disease are important measures in the prevention of this disease. Patients with prosthetic valve endocarditis were infected with antibiotic-resistant organisms and had a higher mortality than those in the medical group (83% versus 20%). Bacterial isolates from three patients with prosthetic valve endocarditis were resistant to methicillin, and two of these three isolates also were resistant to cephalothin by quantitative susceptibility testing. The only patient with prosthetic valve endocarditis to survive was operated upon early in the course of his illness. These observation, coupled with the high mortality in this series and in others, has prompted us to advocate early surgery in prosthetic valve endocarditis.