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 UClike 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. (c) 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.