Summary Background Intestinal tuberculosis (ITB) is less common than Crohn's disease (CD) in Taiwan. Despite the worldwide decline in TB incidence over last several years, the prevalence yet remains high. Therefore, there is a necessity to increase the clinical awareness of this serious health problem. The aim of this study was to investigate the value of clinical methods that may be helpful in distinguishing CD from ITB. Methods Eighty‐five patients, 67 and 18 patients diagnosed with CD and ITB, respectively, from January 2000 to April 2015 at Mackay Memorial Hospital, Taipei were included. The clinical, laboratory, endoscopic, and histological characteristics were reviewed retrospectively. Results CD patients (33 ± 13 years) were younger than ITB patients (57 ± 21 years) (p = 0.103). The incidences of hematochezia, abdominal pain, diarrhea, fever, and weight loss were not significantly different (p = 0.388, p = 0.699, p = 0.751, p = 0.468, and p = 0.611, respectively). The hemoglobin, platelet, and C‐reactive protein (CRP) levels were also not significantly different (p = 0.388, p = 0.440, and p = 0.330, respectively). The endoscopic features of aphthous ulcer and cobblestone appearance were seen more often in CD patients (p = 0.043 and p = 0.010, respectively). Rectal lesions (29.9 vs. 0%; p = 0.020) were seen only in CD patients. Patulous ileocecal valve was specifically seen in ITB patients (p = 0.006). The histological features of granuloma, cryptitis and crypt abscess, and fissure formation were not significantly different (p = 0.377, p = 0.293, and p = 0.212, respectively). Conclusions The endoscopic features of aphthous ulcerations, cobblestone appearance, and rectal involvement in CD and of patulous ileocecal valve in ITB, along with clinical treatment follow‐up, tend to be useful diagnostic characteristics differentiating CD and ITB. Copyright © 2017, The Gastroenterological Society of Taiwan, The Digestive Endoscopy Society of Taiwan and Taiwan Association for the Study of the Liver.