Background and Aim: Differentiating Crohn’s disease from intestinal tuberculosis often challenges clinicians in countries where tuberculosis and Crohn’s disease coexist. The aim of this study was to screen out clinical, endoscopic and histological features which may be helpful in distinguishing Crohn’s disease from intestinal tuberculosis. Methods: 43 patients with a confirmed diagnosis of intestinal tuberculosis and 53 patients with Crohn’s disease were recruited for this study. Their clinical, endoscopic and histological features were subjected to univariate and multivariate analyses. Results: On univariate analysis, the features of hematochezia, intestinal obstruction, fistula, oral ulcers, longitudinal ulcers, cobblestone appearance and pseudopolyps were more common in Crohn’s disease than in intestinal tuberculosis (p < 0.05). The features of night sweats, concomitant pulmonary tuberculosis, positive tuberculin skin test, positive antibody to tuberculosis, abdominal lymphadenopathy, ascites, transverse ulcers, patulous ileocecal valve, and granulomas were more common in intestinal tuberculosis than in Crohn’s disease (p < 0.05). Granulomas exceeding 300 µm in maximal diameter, more than five granulomas per section, and confluent granulomas were more frequently identified in intestinal tuberculosis than in Crohn’s disease (p < 0.05). On further multivariable logistic regression analysis, night sweats (OR 0.1, CI 0.02–0.1), longitudinal ulcers (OR 35.5, CI 1.8–683.2), and granulomas (OR 0.02, CI 0.002–0.2) were found to be significant predictors in differentiating Crohn’s disease from intestinal tuberculosis. Receiver-operating characteristic (ROC) analysis was performed on the scores of patients from the final multivariate logistic model, and the area under the ROC curve was 0.8642 (95% CI 0.79–0.94). Conclusions: Night sweats, longitudinal ulcers and granulomas were the most important features to differentiate Crohn’s disease from intestinal tuberculosis.