Staphylococcus aureus is a common cause of bacterial infections in patients infected with human immunodeficiency virus (HIV). We studied 53 male patients who had 57 episodes of S. aureus bacteremia (SAB). The incidence of SAB per 1000 hospitalized patients was 13.2 among HIV-positive male patients and 0.8 among HIV-negative male patients, yielding a 16.5-fold increase in the odds ratio for SAB among HIV-positive male patients. Almost all episodes of SAB were community acquired. Long-term indwelling catheters were the most common predisposing factor. Prior antibiotic use was more frequently associated with SAB in HIV-positive patients than in HIV-negative patients. A trend was seen among HIV-positive patients toward more numerous infections with beta-lactam antibiotic-resistant (i.e., methicillin-resistant) S. aureus, but such patients had similar outcomes, even though they often did not receive vancomycin during the initial 48 hours of treatment. A better understanding of the epidemiology and clinical manifestations of SAB in HIV-positive patients will offer important opportunities for prevention of this frequent complication.