BACKGROUND: Uncertainties remain about the contribution of methicillin resistance to morbidity and mortality associated with bacteremia caused by Staphylococcus aureus. OBJECTIVE: To assess the impact of methicillin resistance on patient outcome after staphylococcal bacteremia. METHODS: We investigated a cohort of 145 patients with methicillin-sensitive S aureus bloodstream infection (MSSA BSI) and 39 patients with methicillin-resistant S aureus bloodstream infection (MRSA BSI) and further performed a pairwise-matched (1:1) case-control study. All patients in the University Hospital of Geneva, Geneva, Switzerland, with clinically significant staphylococcal bacteremia between January 1, 1994, and December 31, 1995, were included in the study. For the case-control study, cases were defined as patients with MRSA BSI; control patients with MSSA BSI were selected in a stepwise manner according to the following matching variables: age, sex, number of comorbidities, severity of underlying illness, and prior length of stay in the hospital. Matching was successful for 97% of the cohort. MAIN OUTCOME MEASURE: The in-hospital mortality after staphylococcal bacteremia. RESULTS: In the population-based study, the relative hazard of death among patients with MRSA BSI (n = 39, 14 deaths, 36% fatality rate) compared with patients with MSSA BSI (n = 145, 40 deaths, 28% fatality rate) was 1.1 (95% confidence interval, 0.5-2.1), after adjusting for age and length of stay from admission to the onset of bloodstream infection. Following pairwise matching (n = 38), the in-hospital mortality was 34% in both groups (odds ratio, 1.0; 95% confidence interval, 0.4-2.5). Infection was the probable or definite cause of death in 54% of patients with MRSA BSI and 69% of patients with MSSA BSI who died. CONCLUSION: Methicillin resistance in patients with S aureus bacteremia had no significant impact on patient outcome as measured by in-hospital mortality after adjustment was made for major confounders.