Background Addition of oral antibiotics (OA) to mechanical bowel preparation (MBP) is thought to reduce postoperative morbidity compared to MBP alone. However, data supporting this concept in Crohn’s disease patients undergoing ileocolic resection do not exist. Methods Starting, 2016, all ileocolic resections were performed after preoperative MBP combined with OA consisting of two separate dosages of Metronidazole/Neomycine or Metronidazol/Paramomycine. These patients were compared to previous controls undergoing ileocolic resection after mere MBP (1992–2005). Between, 2005 and, 2016, surgeries were performed without preoperative MBP. Patients undergoing an ileocolic resection without construction of anastomosis (i.e., two staged resection) and patients not receiving MBP were excluded from the study. „Anastomotic complications“ were defined as anastomotic leakage, presence of abscess or peritonitis in direct proximity to anastomosis. Results 312 patients underwent ileocolic resections with construction of an anastomosis:, 159 after MBP only and, 153 after preoperative MBP+OA. Patients in MBP+OA group were older (39 y. vs., 35 y., p=0.001), had penetrating disease less frequently (50% vs., 69%, p=0.001), were on biologicals more frequently (31% vs., 1%, p<0.001), on steroids less frequently (12% vs., 59%, p<0.001), underwent laparoscopic surgery more often (80% vs., 15%, p<0.001), and received preoperative parenteral nutrition more often (16% vs., 7%, p=0.033). Patients receiving OA were not able to complete MBP more often (19% vs., 9%, p=0.009). By the multivariate analysis, addition of OA to MBP was associated with a significant reduction of anastomotic complication rate (3% vs., 11%, Hazard ratio, 0.24, p=0.036). Weight loss and steroids were associated with an increased anastomotic morbidity. Conclusion Oral antibiotics added to MBP further improve the anastomotic healing in Crohn’s disease patients undergoing ileocolic resection, although the study has demonstrated an apparent time bias. Further research is needed to clarify whether OA without MBP are as protective as MBP+OA.