Patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at increased risk for invasive infection compared with noncolonized patients; however, the magnitude of risk for MRSA surgical site infection (SSI) is unclear. To aid in planning of infection prevention strategies, we sought to assess the incidence of MRSA SSI in MRSA carriers. We conducted a retrospective cohort study at our tertiary care center of inpatients who underwent MRSA polymerase chain reaction (PCR) screen of the nares within 30 days before a National Healthcare Safety Network principal procedure between April 2008 and July 2010. The rate of MRSA SSI was 1.86% in the MRSA PCR-positive group (n = 431) and 0.20% in the MRSA PCR-negative group (n = 9432). Multivariate analysis identified MRSA PCR-positive status as an independent risk factor for MRSA SSI (odds ratio, 9.20; 95% confidence interval, 3.81-20.47; P < .0001); other risk factors included duration of surgery ≥137 minutes, American Society of Anesthesiologists score ≥3, and abdominal surgery. Surgical patients with a positive nasal MRSA PCR screen had a 9-fold greater odds of developing a subsequent MRSA SSI compared with patients with a negative nasal MRSA PCR screen. The incidence of MRSA SSI in PCR-positive patients was low (1.86%), however, and identifying subsets of patients at greatest risk for SSI may help target decolonization and other interventions.