Background: The incidence of surgical site infection (SSI) is becoming a key component of standard measures of quality of performance. We hypothesized that institutional implementation of a protocol targeting known risk factors would reduce the incidence of SSI associated with intra-abdominal surgery. Methods: Beginning in June 2004, a quality control initiative was implemented to prevent SSI in patients undergoing intra-abdominal surgical procedures at an academic medical center. This protocol included administration of the proper prophylactic antibiotic 0-60 minutes before incision, continued antibiotic administration for ≤24 hours, and maintenance of intraoperative normothermia (≥36°C), along with good glycemic control (goal<200 mg/dL 48 h postoperatively) in diabetic patients. Baseline data collected during the initial four months of protocol development (379 patients) were compared with data collected during the last four months of the 11-month study period (390 patients). Results: Compliance with antibiotic selection increased from 89 percent to 97 percent (p ≤ 0.05). Compliance with timeliness of administration improved from 89 percent to 97 percent (p ≤ 0.05), whereas cessation of perioperative antibiotics within 24 hours remained constant at 93 and 92 percent, respectively. The incidence of hypothermia fell from 15 percent to 10 percent (p = 0.27). The 30-day incidence of SSI improved from 9.2 percent to 5.6 percent (p = 0.07). Conclusion: The implementation of a prevention protocol resulted in a substantial trend toward a reduction in the incidence of SSI. These data support the use of protocol implementation as a cost-effective method of reducing perioperative infectious morbidity associated with intra-abdominal surgery.