To determine the median response time to therapy with vancomycin alone or with vancomycin plus rifampin in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis. Cohort analysis of a randomized study. University medical center. Forty-two consecutive patients with MRSA endocarditis were randomly assigned to receive either vancomycin (group I) or vancomycin plus rifampin (group II) for 28 days. Clinical signs and symptoms were recorded, and blood cultures were obtained daily to determine the duration of bacteremia. The median duration of bacteremia was 9 days (7 days for group I and 9 days for group II). The median duration of fever for all patients and for each treatment group was 7 days. Six patients failed therapy, including three patients who died 5, 6, and 9 days after therapy was started, respectively. The other three patients who failed therapy required valve surgery on days 2, 22, and 27, respectively. Although patients had sustained bacteremia, no unusual complications were seen in either treatment group, and most patients responded to continued antibiotic therapy. Slow clinical response is common among patients with MRSA endocarditis who are treated with vancomycin or vancomycin plus rifampin. Nevertheless, few complications appear to be related solely to this sustained bacteremia.