Background: The differentiation between Ulcerative Colitis (UC) and Crohn's Disease (CD) is an important issue for choosing the appropriate treatment. Endoscopic Ultrasonography (EUS) has been used to distinguish different layers of the gastrointestinal wall. We performed this study to evaluate the accuracy of EUS in differentiating colonic UC from CD compared to standard tests (colonoscopy, pathology, imaging, and clinical presentation). Methods: This is a prospective, single-blinded diagnostic accuracy study, on 70 patients (30 UC, 30 CD, and 10 healthy controls). After obtaining informed consent, patients underwent a complete workup and were referred to an endosonographist who was blind to the diagnosis. The thickness of mucosa, submucosa and the total wall (TWT) of mid-sigmoid colon were measured by Pentax radial echoendoscope EPKI-7000 with Avius Hitachi ultrasound system (Japan). Statistical analyses were performed using the SPSS statistical software (v23). Statistical significance was considered if P-values were less than 0.05. Results: Our study revealed a sensitivity of 100% (90.7-100%) and specificity of 90.9% (70.8-98.8%) for EUS to differentiate UC and CD compared to standard diagnostic tests. Mean mucosal thickness in patients with UC was significantly greater than patients with CD, while, the mean sub-mucosal thickness was significantly greater in patients with CD (p<0.001). The sensitivity and specificity of mean mucosal thickness for differentiating UC from CD and controls were 92.3% and 88.6% with a cut-off point of 1.1 mm (p<0.001). Moreover, sensitivity and specificity of mean submucosal thickness for differentiating CD from UC and controls were 100% and 86.1% with a cut-off point of 1.08 mm (p<0.001). Conclusion: EUS can be used as an efficient modality with acceptable accuracy to differentiate Crohn's disease and Ulcerative Colitis and to determine disease activity.

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