Background: Before elective colectomy, many advocate mechanical bowel preparation with oral antibiotics, whereas enhanced recovery pathways avoid mechanical bowel preparations. The optimal preparation for right versus left colectomy is also unclear. We sought to determine which strategy for bowel preparation decreases surgical site infection (SSI) and anastomotic leak (AL). Methods: Elective colectomies from the National Surgical Quality Improvement Program colectomy database (2012–2015) were divided by (1) type of bowel preparation: no preparation (NP), mechanical preparation (MP), oral antibiotics (PO), or mechanical and oral antibiotics (PO/MP); and (2) type of colonic resection: right, left, or segmental colectomy. Univariate and multivariate analyses identified predictors of SSI and AL, and their risk-adjusted incidence was determined by logistic regression. Results: When analyzed as the odds ratio compared with NP, the PO and PO/MP groups were associated with a decrease in SSI (PO = 0.70 [0.55–0.88] and PO/MP = 0.47 [0.42–0.53]; P <.01). Use of PO/MP was associated with a decrease in SSI across all types of resections (right colectomy = 0.40 [0.33–0.50], left colectomy = 0.57 [0.47–0.68], and segmental colectomy = 0.43 (0.34–0.54); P <.01). Similarly, use of PO/MP was associated with a decrease in AL in left colectomy = 0.50 ([0.37–0.69]; P <.01) and segmental colectomy = 0.53 ([0.36–0.80]; P <.01). Conclusion: Mechanical bowel preparation with oral antibiotics is the preferred preoperative preparation strategy in elective colectomy because of decreased incidence of SSI and AL.