Background: As surgical resection is not curative in Crohn's disease, postoperative recurrence remains a crucial issue. The selection of patients, according to available risk factors, remains disappointing in clinical practice highlighting the need for better criteria, such as histologic features. Aims: To investigate whether submucosal and myenteric plexitis increase the risk of endoscopic, clinical and surgical postoperative recurrence in Crohn's disease. Methods: From the pathology department database, we retrospectively retrieved the data of all the patients who have undergone ileocolonic resection for Crohn's disease. Two pathologists, blinded from clinical data, reviewed all specimens to evaluate the presence of plexitis at the proximal resection margin. Results: Of the 75 included CD patients, 19 (25.3%) had histological involvement of resection margin. Inflammatory cells count for myenteric and submucosal plexus were performed in 56 patients. In multivariate analysis, the myenteric plexitis was a risk factor for endoscopic postoperative recurrence (HR 8.83 CI95% [1.6-48.6], p = 0.012), and the presence of at least one myenteric lymphocyte (HR 4.02 CI95% [1.4-11.2], p = 0.008) was predictive of clinical postoperative recurrence. We observed no histologic predictor for surgical postoperative recurrence. Conclusion: Myenteric plexitis in proximal margins of ileocolonic resection specimens is independently associated with endoscopic and clinical postoperative recurrence in Crohn's disease.