Background: Surgical site infections (SSI) are a common complication after colorectal surgery. An infection prevention bundle (IPB) was implemented to improve outcomes. Study Design: A standardized IPB that included the administration of oral antibiotics with a mechanical bowel preparation, preoperative shower with chlorhexidine, hair removal and skin preparation in holding, antibiotic wound irrigation, and a “clean-closure” protocol was implemented in January 2013. Data from the American College of Surgeons NSQIP were analyzed at a single academic institution to compare pre-IPB and post-IPB SSI rates. In January 2014, a prospective database was implemented to determine compliance with individual IPB elements and their effect on outcomes. Results: For the 24 months pre-IPB, the overall SSI rate was 19.7%. During the 30 months after IPB implementation, the SSI rate decreased to 8.2% (p < 0.0001). A subset of 307 patients was identified in both NSQIP and our prospective compliance databases. Elements of IPB associated with decreased SSI rates included preoperative shower with chlorhexidine (4.6% vs 16.2%; p = 0.005), oral antibiotics (3.4% vs 15.4%; p < 0.001), and mechanical bowel preparation (4.4% vs 14.3%; p = 0.008). Patients who received a full bowel preparation of both oral antibiotics and a mechanical bowel preparation had a 2.7% SSI rate compared with 15.8% for all others (p < 0.001). On multivariate analysis, full bowel preparation was independently associated with significantly fewer SSI (adjusted odds ratio 0.2; 95% CI 0.1 to 0.9; p = 0.006). Conclusions: Implementation of an IPB was successful in decreasing SSI rates in colorectal surgery patients. The combination of oral antibiotics with a mechanical bowel preparation was the strongest predictor of decreased SSI.