Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. Objective: To determine the relationship between oral antibiotic bowel preparation (OABP) and surgical site infection (SSI) rates in a national colectomy cohort. Background: OABP for elective colorectal surgery has fallen out of favor. Large cohort studies show that OABP is associated with a 50% reduction in SSI after colectomy. Methods: A retrospective analysis of the National Surgical Quality Improvement Program colectomy cohort from 2011 to 2012 was performed to examine the association between use of OABP and outcomes of SSI, length of stay (LOS), and readmission after elective colectomy. Univariate and multivariable analyses for SSI were performed. Results: The cohort included 8415 colorectal operations of which 5291 (62.9%) had a minimally invasive surgical (MIS) approach. Overall, 25.6% had no bowel preparation, 44.9% had mechanical bowel preparation (MBP) only, and 29.5% received OABP. The SSI rate was 11.1%, and it varied by preparation type: 14.9% no preparation, 12.0% MBP, and 6.5% OABP (P < 0.001). OABP group had significantly shorter hospital LOS: (median = 4, interquartile range: 3-6) versus other preparations (median LOS = 5) (P < 0.001). Readmission rates were lowest in OABP (8.1%) and highest in the no preparation group (11.8%). Multivariable logistic regressions found OABP associated with lower SSI [adjusted odds ratio (ORadj) = 0.46, 95% confidence interval (CI): 0.36-0.59]. Stratified models found OABP protective for SSI for both open procedures (ORadj = 0.40, 95% CI: 0.30-0.53) and MIS procedures (ORadj = 0.48, 95% CI: 0.36-0.65). Conclusions: OABP is associated with reduced SSI rates, shorter LOS, and fewer readmissions. Adoption of OABP before elective colectomy would reduce SSI without effecting LOS. The practice of MBP alone should be abandoned.