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Background and study aims Artificial intelligence (AI) in gastrointestinal endoscopy is developing very fast. Computer-aided detection of polyps and computer-aided diagnosis (CADx) for polyp characterization are available now. This study was performed to evaluate the diagnostic performance of a new commercially available CADx system in clinical practice. Patients and methods This prospective, non-randomized study was performed at a tertiary academic endoscopy center from March to August 2022. We included patients receiving a colonoscopy. Polypectomy had to be performed in all polyps. Every patient was examined concurrently by an endoscopist and AI using two opposing screens. The AI system, overseen by a second observer, was not visible to the endoscopist. The primary outcome was accuracy of the AI classifying the polyps into "neoplastic" and "non-neoplastic." The secondary outcome was accuracy of the classification by the endoscopists. Sessile serrated lesions were classified as neoplastic. Results We included 156 patients (mean age 65; 57 women) with 262 polyps ≤10 mm. Eighty-four were hyperplastic polyps (32.1%), 158 adenomas (60.3%), seven sessile serrated lesions (2.7%) and 13 other entities (normal/inflammatory colonmucosa, lymphoidic polyp) (4.9%) on histological diagnosis. Sensitivity, specificity and accuracy of AI were 89.70% (95% confidence interval [CI]: 84.02%-93.88%), 75.26% (95% CI: 65.46%-83.46%) and 84.35% (95% CI:79.38%-88.53%), respectively. Sensitivity, specificity and accuracy for less experienced endoscopists (2-5 years of endoscopy) were 95.56% (95% CI: 84.85%-99.46%), 61.54% (95% CI: 40.57%-79.77%) and 83.10% (95% CI: 72.34%-90.95%) and for experienced endoscopists 90.83% (95% CI: 84.19%-95.33%), 71.83% (95% CI: 59.90%-81.87%) and 83.77% (95% CI: 77.76%-88.70%), respectively. Conclusion Accuracy for polyp characterization by a new commercially available AI system is high, but does not fulfill the criteria for a "resect-and-discard" strategy., Competing Interests: Conflict of Interest Oliver Pech has received speaker honorarium from Medtronic Norgine, Olympus and Fujifilm. The remaining authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)