Objective.To quantify the clinical impact of methicillin‐resistance in Staphylococcus aureus causing infection complicated by bacteremia in adult patients, while controlling for the severity of patients’ underlying illnesses.

Design.Retrospective cohort study from October 1, 1995, through December 31, 2003.

Patients and Setting.A total of 438 patients with S. aureus infection complicated by bacteremia from a single Veterans Affairs healthcare system.

Results.We found that 193 (44%) of the 438 patients had methicillin‐resistant S. aureus (MRSA) infection and 114 (26%) died of causes attributable to S. aureus infection within 90 days after the infection was identified. Patients with MRSA infection had a higher mortality risk, compared with patients with methicillin‐susceptible S. aureus (MSSA) infections (relative risk, 1.7 [95% confidence interval, 1.3‐2.4]; ), except for patients with pneumonia (relative risk, 0.7 [95% confidence interval, 0.4‐1.3]). Patients with MRSA infections were significantly older ( ), had more underlying diseases ( ), and were more likely to have severe sepsis in response to their infection ( ) compared with patients with MSSA bacteremia. Patients who died within 90 days after S. aureus infection was identified were significantly older ( ) and more likely to have severe sepsis ( ) and pneumonia ( ), compared with patients who survived. After adjusting for age as a confounder, comorbidities, and pneumonia as an effect modifier, S. aureus infection–related mortality remained significantly higher in patients with MRSA infection than in those with MSSA infection, among those without pneumonia (hazard ratio, 1.8 [95% confidence interval, 1.2‐3.0]); .

Conclusions.The results of this study suggest that patients with MRSA infections other than pneumonia have a higher mortality risk than patients with MSSA infections other than pneumonia, independent of the severity of patients' underlying illnesses.