We prospectively studied all cases of Staphylococcus aureus bacteremia that occurred during an extensive outbreak of methicillin-resistant S. aureus (MRSA) in our hospital over a 4-year period (January 1990 through September 1993). We report the results of a comparative analysis of the clinical characteristics and mortality rates among patients with nosocomial bacteremia caused by MRSA (84 cases) or methicillin-susceptible S. aureus (MSSA; 100 cases). The patients with MRSA bacteremia were older than those with MSSA bacteremia (69 years vs. 54 years, respectively; P < .01) and were more likely than those with MSSA bacteremia to have the following predisposing factors: a prolonged hospitalization (32 days vs. 14 days, respectively; P < .01); prior antimicrobial therapy (61% vs. 34%, respectively; P < .01); urinary catheterization (58% vs. 27%, respectively; P < .01); nasogastric tube placement (31% vs. 13%, respectively; P < .01); and prior surgery (45% vs. 31%, respectively; P = .05). Multivariate analysis with use of the stepwise logistic regression method showed a relationship between mortality and the following variables: methicillin resistance (odds ratio [OR], 3), meningitis (OR, 13), and inadequate treatment (OR, 11).