Background: Mucosal healing (MH) is the key aim of the treat-to-target strategy for patients with Crohn’s disease (CD). The efficacy of infliximab (IFX) on MH in different ileocolonic segments is unclear. The aim of this study was to investigate endoscopic MH in different ileocolonic segments in patients with CD who received IFX treatment. Methods: A retrospective, single-center study was performed in patients with active ileocolonic CD between January 2012 and December 2018. All patients underwent IFX treatment for at least 30 weeks. The MH of five ileocolonic segments was assessed by the Simple Endoscopic Score for CD (SES-CD) at baseline, 14/22 weeks and 30/38 weeks. The SES-CD values were analyzed by a mixed-effects model after the correction for confounding factors. Results: A total of 101 eligible patients were included. The baseline endoscopic severity was similar across segments. At 30/38 weeks, the greatest changes in the SES-CD ulcer size and ulcerated surface subscores were −94.29% and −94.32% both in the transverse colon ( p