OBJECTIVES:To clarify whether bowel preparation use or its individual components mechanical bowel preparation (MBP)/oral antibiotics impact specific outcomes after colorectal surgery. METHODS:National Surgical Quality Improvement Program–targeted colectomy data initiated in 2012 capture information on the use/type of bowel preparation and colorectal-specific complications. For patients undergoing elective colorectal resection, the impact of preoperative MBP and antibiotics (MBP+/ABX+), MBP alone (MBP+/ABX−), and no bowel preparation (no-prep) on outcomes, particularly anastomotic leak, surgical site infection (SSI), and ileus, were evaluated using unadjusted/adjusted logistic regression analysis. RESULTS:Of 8442 patients, 2296 (27.2%) had no-prep, 3822 (45.3%) MBP+/ABX−, and 2324 (27.5%) MBP+/ABX+. Baseline characteristics were similar; however, there were marginally more patients with prior sepsis, ascites, steroid use, bleeding disorders, and disseminated cancer in no-prep. MBP with or without antibiotics was associated with reduced ileus MBP+/ABX+odds ratio (OR) = 0.57, 95% confidence interval (CI)0.48–0.68; MBP+/ABX−OR = 0.78, 95% CI0.68–0.91 and SSI MBP+/ABX+OR = 0.39, 95% CI0.32–0.48; MBP+/ABX−OR = 0.80, 95% CI0.69–0.93 versus no-prep. MBP+/ABX+ was also associated with lower anastomotic leak rate than no-prep OR = 0.45 (95% CI0.32–0.64). On multivariable analysis, MBP with antibiotics, but not without, was independently associated with reduced anastomotic leak (OR = 0.57, 95% CI0.35–0.94), SSI (OR = 0.40, 95% CI0.31–0.53), and postoperative ileus (OR = 0.71, 95% CI0.56–0.90). CONCLUSIONS:These data clarify the near 50-year debate whether bowel preparation improves outcomes after colorectal resection. MBP with oral antibiotics reduces by nearly half, SSI, anastomotic leak, and ileus, the most common and troublesome complications after colorectal surgery.