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Background: Post-polypectomy surveillance intervals are currently determined based on pathology results., Aim: To evaluate a polyp-based resect and discard model that assigns surveillance intervals based solely on polyp number and size., Methods: Patients undergoing elective colonoscopies at the Montreal University Medical Center were enrolled prospectively. The polyp-based strategy was used to assign the next surveillance interval using polyp size and number. Surveillance intervals were also assigned using optical diagnosis for small polyps (< 10 mm). The primary outcome was surveillance interval agreement between the polyp-based model, optical diagnosis, and the pathology-based reference standard using the 2020 United States Multi-Society Task Force guidelines. Secondary outcomes included the proportion of reduction in required histopathology evaluations and proportion of immediate post-colonoscopy recommendations provided to patients., Results: Of 944 patients (mean age 62.6 years, 49.3% male, 933 polyps) were enrolled. The surveillance interval agreement for the polyp-based strategy was 98.0% [95% confidence interval (CI): 0.97-0.99] compared with pathology-based assignment. Optical diagnosis-based intervals achieved 95.8% (95%CI: 0.94-0.97) agreement with pathology. When using the polyp-based strategy and optical diagnosis, the need for pathology assessment was reduced by 87.8% and 70.6%, respectively. The polyp-based strategy provided 93.7% of patients with immediate surveillance interval recommendations vs 76.1% for optical diagnosis., Conclusion: The polyp-based strategy achieved almost perfect surveillance interval agreement compared with pathology-based assignments, significantly reduced the number of required pathology evaluations, and provided most patients with immediate surveillance interval recommendations., Competing Interests: Conflict-of-interest statement: Mahsa Taghiakbari, Celia Hammar, Mira Frenn, Roupen Djinbachian, Heiko Pohl, Erik Deslandres, Simon Bouchard, and Mickael Bouin have no conflicts of interest relevant to this paper to disclose. Daniel von Renteln is supported by the "Fonds de Recherche du Québec Santé" career development award and has received research funding from ERBE, Ventage, Pendopharm and Pentax and is a consultant for Boston Scientific and Pendopharm. The findings, statements, and views expressed are those of the authors and do not represent the views of the Department of Veterans Affairs or the United States Government., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)