The role of rectal carriage of Staphylococcus aureus as a risk factor for nosocomial S. aureus infections in critically ill patients has not been fully discerned. Nasal and rectal swabs for S. aureus were obtained on admission and weekly thereafter until discharge or death from 204 consecutive patients admitted to the surgical intensive care unit and liver transplant unit Overall, 49.5% (101 of 204) of the patients never harbored S. aureus, 21.6% (44 of 204) were nasal carriers only, 3.4% (7 of 204) were rectal carriers only, and 25.5% (52 of 204) were both nasal and rectal carriers. Infections due to S. aureus developed in 15.7% (32 of 204) of the patients; these included 3% (3 of 101) of the non-carriers, 18.2% (8 of 44) of the nasal carriers only, 0% (0 of 7) of the rectal carriers only, and 40.4% (21 of 52) of the patients who were both nasal and rectal carriers (P - .001). Patients with both rectal and nasal carriage were significantly more likely to develop S. aureus infection than were those with nasal carriage only (odds ratio, 3.9; 95% confidence interval, 1.18 to 7.85; P= .025). By pulsed-field gel electrophoresis, the infecting rectal and nasal isolates were clonally identical in 82% (14 of 17) of the patients with S. aureus infections. Rectal carriage represents an underappreciated reservoir for S. aureus in patients in the intensive care unit and liver transplant recipients. Rectal plus nasal carriage may portend a greater risk for S. aureus infections in these patients than currently realized.