Background: There is significant variation in the use of mechanical bowel preparation and oral antibiotics prior to left-sided elective colorectal surgery. There has been no consensus internationally. Methods: This was a retrospective analysis of the 2015 American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into four groups: those who had mechanical bowel preparation with oral antibiotics, mechanical bowel preparation alone, oral antibiotics alone and no preparation. The main outcome measures included overall, superficial, deep and organ/space surgical site infections. Secondary outcomes included anastomotic leak, ileus and rate of Clostridium difficile. Results: A total of 5729 patients were included for analysis. The overall surgical site infection rate (any superficial, deep or organ/space infection) was significantly lower in the mechanical bowel preparation and oral antibiotics approach when compared to no preparation (OR = 0.46, 95% CI 0.36–0.59, P < 0.0001). On multivariable logistic regression analysis, mechanical bowel preparation with oral antibiotics maintained a lower risk of overall surgical site infections. MBP and OAB also had a protective effect on anastomotic leak in both the laparoscopic and open cohorts (laparoscopic multivariable adjusted OR = 0.42 (0.19–0.94), P = 0.035; open multivariable adjusted OR = 0.3 (0.12–0.77), P = 0.012). Mechanical bowel preparation alone and oral antibiotics alone was not associated with a significant decrease in surgical site infections. There was no increase in C. difficile occurrences with the use of oral antibiotics. Conclusion: Mechanical bowel preparation with oral antibiotics significantly minimised surgical site infections and anastomotic leak following both laparoscopic and open left-sided restorative colorectal surgery. Mechanical bowel preparation alone did not reduce surgical site infections. There was a trend to reduction in surgical site infections with oral antibiotics alone.