Background While the effect of anti-TNFs on postoperative outcomes in patients with Crohn's disease (CD) has been widely studied, the impact of vedolizumab and ustekinumab on the risk of postoperative complications remains poorly known. Methods All consecutive patients who underwent intestinal resection for CD between July 2014 and April 2022 within 22 French centers were included in a retrospective cohort. The risk of early post-operative complications (≤30days) in patients exposed to biologics was compared to patients not exposed by logistic regression and propensity score-matched analysis adjusted for age, previous intestinal resection, corticosteroids or immunosuppressants exposure, disease activity, presence of abscess, urgent surgery and initial stoma (preoperative contra-indication to anastomosis). Results Among the 1201 patients included, respectively 491 (41%), 76 (6.3%) and 57 (4.7%) were exposed to anti-TNFs, ustekinumab, or vedolizumab within six months before surgery. A total of 317 (26.4%) patients had at least one complication of which 123 (38%) were considered as severe (DINDO III/IV). New surgery was necessary in 69 (5.7%) patients and secondary stoma in 23 (1.9%). Three deaths were observed (0.25%). The rates of overall complications in patients not exposed to biologics, exposed to anti-TNFs, ustekinumab or vedolizumab were respectively 26.1%, 25.1%, 34.7% and 29.8%. The risks of intra-abdominal infectious complications in these four groups were respectively 13.5%, 11.1%, 13.3% and 8.8%. In multivariate analysis, age [OR, 1.02 (1.01-1.04); p=0.004], disease activity [OR, 8.36 (1.79 – 149); p=0.037], the presence of an abscess [OR, 2.01 (1.25-3.20); p=0.004] and initial stoma [OR, 1.70 (1.10 –2.61); p=0.016] were significantly associated with intra-abdominal infectious complications. Conversely, preoperative enteral nutrition [OR, 0.12 (0.01 -0.59); p=0.040] was associated with a reduction in this risk. Exposure to anti-TNFs [OR, 0.80 (0.51-1.24); p=0.31], ustekinumab [OR, 1.17 (0.39-3.51); p=0.78] and vedolizumab [OR, 1.28 (0.32-5.17); p=0.72] within the 3 months before surgery were not associated with the risk of intra-abdominal infectious complications. Similar results were observed in patients exposed to these treatments in the month before surgery. Conclusion In this large cohort, a quarter of patients operated on for CD presented an early postoperative complication and 10% a severe complication. Preoperative exposure to anti-TNFs, vedolizumab or ustekinumab was not associated with an increased risk of early postoperative complications. Preoperative enteral nutrition was associated with a reduced risk of intra-abdominal infectious complication.