Background Evaluating the impact of steroid or immunosuppressants (SI) therapy prior to colectomy in Crohn's disease (CD) patients on postoperative septic and colectomy-specific outcomes using the American College of Surgeons (ACS)-National Surgical Quality Improvement Program (NSQIP)-targeted colectomy database. Methods All CD patients undergoing colectomy were retrieved from the 2012-2013 NSQIP-targeted database. Thirty-day postoperative outcomes were compared for patients who were on steroids or immunosuppressants (SI) within the 30 days prior to colectomy to the others using univariable and multivariable analyses. Results Of 2208 CD patients, 1387 (63%) were on SI. Patients in the SI group were younger, and a greater proportion underwent laparoscopic surgery (p\ 0.05). SI use was associated with a higher rate of sepsis (7.6 vs. 5.2%), anastomotic leak (5.6 vs. 3.5%), and return to operating room (6.8 vs. 3.3%). On multivariable analysis, SI was associated with sepsis, septic shock, and anastomotic leak [odds ratio = 1.58, 95% confidence interval 1.09-2.27]. Conclusions These results suggest that SI use within 30 days of colectomy is associated with a higher rate of sepsis and septic shock and anastomotic leak in CD patients. Withholding SI prior to surgery, or the selective use of an ostomy to mitigate the consequences of a leak and hence sepsis need due consideration prior to surgery.