We prospectively evaluated 46 possible risk factors for methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection (SSI) among patients with MRSA carriage in a large intervention study. Of 6,130 study patients, 68 (1.1%) developed MRSA SSI, which occurred a median of 14 days after surgery. Risk factors associated with MRSA SSI were receipt of emergency surgery, presence of comorbid condition, receipt of immunosuppressive therapy, receipt of contaminated surgery, and a surgical duration longer than the 75th percentile. MRSA carriage on admission did not predict MRSA SSI.