In the surgical intensive care unit of a university hospital, we investigated the frequency of and the risk factors for acquisition of methicillin-resistant Staphylococcus aureus (MRSA) during postoperative intra-abdominal infection (pIAI). We conducted a prospective MRSA nasal screening and case evaluation for 17 months among 73 consecutive patients with having pIAI. MRSA pIAI was diagnosed when MRSA was obtained from culture of intraperitoneal fluids. The identity of nasal and peritoneal MRSA strains was assessed by genomic analysis. Twelve patients had MRSA pIAI, representing 21% of all MRSA infections acquired by the 73 patients. An organ system failure score of >/=1 and MRSA nasal carriage prior to pIAI were the independent risk factors for acquisition of MRSA pIAI. Patients with MRSA pIAI had a longer intensive care unit stay and more reoperations than did those free of MRSA pIAI. We conclude that MRSA may be a causative pathogen in pIAI and may be related to nasal colonization.