AimThe role of bowel preparation before colectomy in Crohn's disease patients remains controversial. This retrospective analysis of a prospective cohort study aimed to investigate the clinical outcomes associated with mechanical and antibiotic colon preparation in patients diagnosed with Crohn's disease undergoing elective colectomy.MethodData were collected from the American College of Surgeons National Surgical Quality Improvement Program participant user files from 2016 to 2021. A total of 6244 patients with Crohn's disease who underwent elective colectomy were included. The patients were categorized into two groups: those who received combined colon preparation (mechanical and antibiotic) and those who did not receive any form of bowel preparation. The primary outcomes assessed were the rate of anastomotic leak and the occurrence of deep organ infection. Secondary outcomes included all‐cause short‐term mortality, clinical‐related morbidity, ostomy creation, unplanned reoperation, operative time, hospital length of stay and ileus.ResultsCombined colon preparation was associated with significantly reduced risks of anastomotic leak (relative risk 0.73, 95% CI 0.56–0.95, P = 0.021) and deep organ infection (relative risk 0.68, 95% CI 0.56–0.83, P < 0.001). Additionally, patients who underwent colon preparation had lower rates of ostomy creation, shorter hospital stays and a decreased incidence of ileus. However, there was no significant difference in all‐cause short‐term mortality or the need for unplanned reoperation between the two groups.ConclusionThis study shows that mechanical and antibiotic colon preparation may have clinical benefits for patients with Crohn's disease undergoing elective colectomy.