OBJECTIVE To determine the comparative virulence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S aureus (MSSA) by consideration of predisposing factors and outcomes in patients infected with these organisms in the healthcare setting. METHODS Analysis of an historical cohort of 504 bacteremic patients (316 MSSA and 188 MRSA), examining factors associated with mortality. METHODS A 916-bed, university-affiliated, tertiary referral hospital. RESULTS Risk factors for the development of MRSA include male gender, admission due to trauma, immunosuppression, presence of a central vascular line or an indwelling urinary catheter, and a past history of MRSA infection. Overall mortality was 22%. Death due to bacteremia was significantly greater in the MRSA group (risk ratio, 1.68; P<.05), although these patients were not found to be more likely to die due to underlying disease during treatment of bacteremia. In those patients who recovered from bacteremia, no significant differences for the outcome of death could be determined between the MRSA and MSSA groups. CONCLUSIONS There is a general consensus in the published literature that MRSA bacteremia is more likely to be associated with death, and we confirm this conclusion. However, in contrast to other studies, our MRSA cohort does not appear to be more at risk of death due to underlying disease during treatment for bacteremia. Similarly, the general consensus that MRSA patients have an increased overall mortality was not confirmed in our study. Differences in comorbidities of patients may provide some explanation of these conflicting results, while an alternate explanation is that MRSA strains are more virulent than MSSA in some centers. Perhaps the most plausible explanation is that treatment is provided earlier and in a more aggressive fashion in some centers, leading to an overall lower mortality rate in all staphylococcal bacteremias in these institutions.