Objectives: There are concerns that biologic treatments or immunomodulation may negatively influence anastomotic healing. This study investigates the relationship between these treatments and anastomotic complications after surgery for Crohn's disease. Patients and methods. Retrospective study on 417 operations for Crohn's disease performed at four Danish hospitals in 2000-2007. Thirty-two patients were preoperatively treated with biologics and 166 were on immunomodulation. In total, 154 were treated with corticosteroids of which 66 had prednisolone 20 mg or more. Results: Anastomotic complications occurred at 13% of the operations. There were no difference in patients on biologic treatment (9% vs. 12% (p=0.581)) or in patients on immunomodulation (10% vs. 14% (p=0.263)). Patients on 20 mg prednisolone or more had more anastomotic complications (20% vs. 11% (p=0.04)). Anastomotic complications were more frequent after a colo-colic anastomosis than after an entero-enteric or entero-colic (33% vs. 12% (p=0.013)). Patients with anastomotic complications were older (40 years vs. 35 years (p=0.014)), had longer disease duration (7.5 years vs. 4 years (p=0.04)), longer operation time (155 min vs. 115 min (p=0.018)) and more operative bleeding (200 ml vs. 130 ml (p=0.029)). Multivariate analysis revealed preoperative treatment with prednisolone 20 mg or more, operation time and a colo-colic anastomosis as negative predictors of anastomotic complications. Conclusions: Preoperative biologic treatment or immunomodulation had no influence on anastomotic complications. The study confirms previous findings of corticosteroids and a colo-colic anastomosis as negative predictors and also that surgical complexity, as expressed by bleeding and operation time, may contribute to anastomotic complications. © 2012 Informa Healthcare.