We prospectively studied the relationship of perioperative methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization and subsequent infection in surgical intensive care unit (SICU) patients. In addition, risk factors for MRSA nasal colonization were examined. All patients admitted to the 15-bed SICU between August 1991 and July 1992 had their anterior nares cultured. Cultures positive for S. aureus were subsequently placed on oxacillin-containing plates to screen for methicillin-resistance. Of 484 patients, 19 had MRSA nasal colonization (3.9%). There were five infections in the 19 patients with positive perioperative nasal cultures versus six infections in the remaining 465 patients (P < 0.0001). Immunoblot typing confirmed the concordance of colonizing and infecting strains. Prior exposure to the spinal cord injury center (P < 0.001) and prior antibiotic therapy (P < 0.003) were also significant multivariate risk factors for perioperative nasal colonization. Patients with perioperative MRSA nasal colonization are at significantly increased risk of subsequent postoperative MRSA infection.