Differentiating intestinal Behçet's disease (BD) from Crohn's disease (CD) is highly challenging, as they often mimic each other in terms of clinical manifestations. Endoscopy is an important modality for distinguishing bowel lesions. The study was designed to identify clinical manifestations that are easily confused and to evaluate the efficacy of endoscopy for distinguishing intestinal BD from CD by several overlapping signs.Materials and methods: The data from 111 patients with intestinal BD and 81 patients with CD were retrospectively analyzed. Logistic regression was applied to establish a prediction model based on endoscopic findings for the differential diagnosis. The diagnostic efficacy of endoscopy was verified using the area under the receiver operating characteristic (ROC) curve.Results: Among intestinal BD patients mucocutaneous lesions were the leading clinical manifestations. Gastrointestinal symptoms were common in CD but were rare in intestinal BD (P < 0.001). CD patients with moderate-to-severe activity were more common than intestinal BD patients presenting with equivalent activity (P < 0.05). Independent factors that distinguished intestinal BD from CD were solitary ulcer in the ileocecal area (P < 0.001), perianal abscess (P = 0.049), single segment (P < 0.001), round intestinal ulcer (P = 0.013), intestinal obstruction (P = 0.035), and fistula (P < 0.001). The scores ranged from -2 to 3. The area under the ROC curve was 0.874 (95% CI: 0.823-0.926) (P < 0.001). With a score of 1.5 as the diagnostic cutoff value, the sensitivity and specificity were 76.3% and 80.6%, respectively.Conclusion: Mucosal injuries were rarer in patients with intestinal BD than in those with CD. The differentiation model combining several endoscopy features appeared to be reliable for distinguishing between intestinal BD and CD.