Background Surgical-site infections (SSI), because of MRSA, are a challenge for acute care hospitals. The current study examines the impact of best practices and active surveillance screening for MRSA on reduction of MRSA SSIs. Study Design Beginning February 2007, all admissions to a 761-bed tertiary care hospital were screened for MRSA by nasal swab using polymerase chain reaction-based testing. Positive nasal carriers of MRSA were treated before operation. The subset of patients undergoing procedures that are part of the Surgical Infection Prevention Project were followed for MRSA SSIs. SSI rates (per 100 procedures) were determined using the National Nosocomial Infection Surveillance definitions. MRSA SSI rates were compared before and after the MRSA screening intervention. Differences were analyzed using Fisher's exact test and chi-square with Yate's continuity correction. Where specimens were available, genotyping of MRSA was performed using a commercially available assay. Results After universal MRSA surveillance, 5,094 patients underwent Surgical Infection Prevention Project procedures. The rate of MRSA SSI decreased from 0.23% to 0.09%. The reduction was most pronounced in joint-replacement procedures (0.30% to 0%; p = 0.04). No other differences were statistically significant. Of the seven patients in whom MRSA SSI developed after universal screening, four had positive MRSA screens; none had received preoperative eradication of MRSA. In two of these patients, the genotype of MRSA detected on screening and in SSI was genetically indistinguishable. Conclusions Surveillance for MRSA and eradication of the carrier state reduces the rate of MRSA SSI.