We undertook a study of the characteristics and clinical impact of infections due to methicillin-resistant Staphylococcus aureus (MRSA) after liver transplantation. Of 165 patients who received liver transplants at our institution from 1990 through 1998, 38 (23%) developed MRSA infections. The predominant sources of infection were vascular catheters (39%; n=15), wound (18%; n=7), abdomen (18%; n=7), and lung (13%; n=5). A significant increase in MRSA infections (as a percentage of transplant patients infected per year) occurred over time (P=.0001). This increase was greater among intensive care unit patients (P=.001) than among nonintensive care unit hospital patients (P=.17). Cytomegalovirus seronegativity (P=.01) and primary cytomegalovirus infection were significantly associated with MRSA infections (P=.005). Thirty-day mortality among patients with MRSA infections was 21% (8/38). Mortality was 86% in patients with bacteremic MRSA pneumonia or abdominal infection and 6% in those with catheter-related bacteremia (P=.004). Thus the incidence of MRSA infection has increased exponentially among our liver transplant recipients since 1990. These infections have unique risk factors, time of onset, and a significant difference in site-specific mortality; deep-seated bacteremic infections, in particular, portend a grave outcome.