Preoperative use of biologics has been inconsistently reported to be associated with increased frequency of infectious and surgical anastomotic complications in inflammatory bowel disease patients. We aimed to evaluate the rates of 30-day postoperative morbidity and mortality in Crohn's disease patients exposed preoperatively to biologics. Data were collected from the NSQIP (National Surgical Quality Improvement Program). Crohn's disease patients undergoing open or laparoscopic ileocolectomy were identified using corresponding ICD 10 and CPT Codes from the NSQIP Participant Use Data File (PUF) for 2021. Patients were divided based on the preoperative use of biologics (group 1) and (group 2) for whom no biologics were used. A total of 910 patients (female n = 473; 52%, mean age of 42.3 +/- 16.1) were included. The group 1 patients were significantly younger (40.30 years +/- 15.33) than group 2 (43.58 years +/- 16.8, p = 0.002) and had significantly slightly higher ASA III and IV scores (97.4% vs. 97.2%, p = 0.004). On the other hand, group 2 had a significantly higher prevalence of hypertension (20.2% vs. 12.8%, p = 0.003) and chronic obstructive pulmonary disease (2.6% vs. 0%, p = 0.001). No significant difference in remaining preoperative variables, surgical approach (laparoscopic vs. open), and comorbidities were found between the two groups. Only a significant prevalence of deep vein thrombosis and thromboembolism was found in patients exposed to biologics (1.1% vs. 0%, p = 0.027). Crohn's disease patients undergoing ileocolectomy and exposed preoperatively to biologics did not show a significant increase in 30-day postoperative morbidity and mortality. The outcomes did not support the concept that biological agents increase septic complications.