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Background: Segmental colitis associated with diverticulosis (SCAD) is characterized by a chronic inflammatory response involving the inter-diverticular colonic mucosa, sparing the rectum and the right colon., Aims: to assess the prevalence of SCAD in a CRC screening program and to evaluate the differences in terms of oncological outcomes between SCAD and diverticulosis., Methods: retrospective analysis from a prospectively-maintained database including all subjects undergoing first screening colonoscopy., Results: 1518 patients were included (51.8 % male, mean age 63.48 ± 6.39). Adenomas were detected in 638 patients (ADR 42 %), CRC was diagnosed in 5.7 %. Diverticulosis was described in 37.5 %, while SCAD in 4.5 %. Among them, 69.6 % presented crescentic-fold disease, 20.3 % mild-to-moderate UC-like pattern, 8.7 % CD-like pattern and 1.4 % severe UC-like pattern. When SCAD was compared to uncomplicated/asymptomatic diverticulosis (501 patients), we found no differences in terms of gender (p = 0.46) or age (p = 0.47). Interestingly, the use of anticoagulant/antiplatelet (p = 0.79), anti-hypertensive (p = 0.89) or anti-hyperglycaemic drugs (p = 0.52) had no effect on SCAD onset as compared to diverticulosis. SCAD patients had significant lower rate of adenomas (ADR 31.9% vs 47.3 %, p = 0.018, OR 0.52, 95 %CI 0.31-0.89), and lower-but not significant-rate of CRC (1.4% vs 6.2 %, p = 0.14, OR 0.22, 95 %CI 0.02-1.66)., Conclusions: SCAD can be diagnosed in about 5 % of population undergoing screening colonoscopy and in 12 % of those with diverticulosis. SCAD seems to be associated with a reduced rate of adenomas or CRC as compared with diverticulosis., Competing Interests: Conflict of interest The authors declare no conflict of interest regarding the current manuscript., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)