Abstract Background The best management after ileocolonic resection is still unknown in Crohn’s disease (CD). We compared step-up and top-down approaches to prevent short and long-terms postoperative recurrences in CD patients. Methods From a comprehensive database, consecutive CD patients who underwent intestinal resection (2014–2021) were included. Top-down (biologics started within the first month after surgery) or step-up strategies (no biologic between surgery and colonoscopy at, 6 months) were performed with systematic colonoscopy at, 6 months and therapeutic escalation if Rutgeerts index was ≥i2a (endoscopic postoperative recurrence). Propensity score analysis (Inverse probability of treatment weighting) was applied for each comparison adjusted on the following parameters: gender, prior history of bowel resection, smoking habits, CD location, CD behaviour, resection length >, 30 cm, age and the number of biologics before surgery. Results Among, 115 CD patients, top-down was the most effective strategy to prevent endoscopic postoperative recurrence (Rutgeerts index ≥ i2a) (46.8% vs, 65.9%, p=0.042) and to achieve complete endoscopic remission (Rutgeerts index = i0) (45.3% vs, 19.3%, p=0.004) at, 6 months. The median time of follow-up (ending at the time first progression of bowel damage or last follow-up) was, 41.9 months [21.4–76.2]. We did not observe any significant difference between the two groups regarding clinical postoperative recurrence (hazard ratio (HR) = 0.86 [0.44–1.66], p=0.66) and progression of bowel damage (HR = 0.81 [0.63–1.06], p=0.12). Endoscopic postoperative recurrence (Rutgeerts index ≥ i2a) at, 6 months was associated with increased risk of clinical postoperative recurrence (HR = 1.97 [1.07–3.64], p, 0.029) and progression of bowel damage (HR = 3.33 [1.23–9.02], p=0.018). Among the subgroup without endoscopic postoperative recurrence (Rutgeerts index = i0 or i1) at, 6 months, the risks of clinical postoperative recurrence and progression of bowel damage were significantly improved in the top-down group compared to step-up (HR = 0.59 [0.37–0.94], p = 0.025) and HR = 0.73 [0.63–0.83], p<0.001, respectively). In contrast, when focusing on patients experiencing endoscopic postoperative recurrence (Rutgeerts index ≥ i2a) at, 6 months, top-down approach was associated with higher likelihood of clinical postoperative recurrence (HR = 1.92 [1.02–3.59], p = 0.042) and progression of bowel damage (HR = 1.58 [1.03–2.42], p = 0.035). Conclusion Top-down strategy should be preferred to step-up approach to prevent endoscopic postoperative recurrence as well as clinical postoperative recurrence and progression of bowel damage in most of the patients with Crohn’s disease after bowel resection.