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OBJECTIVES The European Society of Cardiology endorsed SCORE2 to assess cardiovascular risk. The aim of this observational, retrospective study was to assess whether SCORE2 is associated with colorectal neoplasia in an asymptomatic screening population. Further, we evaluated if SCORE2 predicts tumor-related mortality. METHODS We included 3408 asymptomatic patients who underwent a screening colonoscopy. We calculated SCORE2 for each participant and stratified patients according to their predicted 10-year risk of cardiovascular disease: SCORE2 0-4.9%, SCORE2 5-9.9%, and SCORE2 ≥ 10%. We assessed the association between SCORE2 as a continuous variable, the presence of colorectal neoplasia using multilevel logistic regression, and SCORE2 and mortality using Cox regression. RESULTS In total, 1537 patients had a SCORE2 of 0-4.9%, 1235 a SCORE2 of 5-9.9%, and 636 a SCORE2 ≥ 10%. The respective rates of colorectal neoplasia were 20%, 37%, and 44%. SCORE2 was associated with the presence of any (OR 1.11 95%CI 1.09-1.12; p < 0.001) and advanced colorectal neoplasia (OR 1.06 95%CI 1.08-1.13; p < 0.001) in univariate analysis. After multivariable adjustment (age, sex, family history, and metabolic syndrome) a higher SCORE2 remained associated with higher odds for any (aOR 1.04 95%CI 1.02-1.06; p = 0.001) and advanced (aOR 1.06 95%CI 1.03-1.10; p < 0.001) colorectal neoplasia. SCORE2 was associated with both all-cause (HR 1.11 95%CI 1.09-1.14; p < 0.001) and tumor-related mortality (HR 1.10 95%CI 1.05-1.14; p < 0.001). CONCLUSIONS We found that SCORE2 is associated with the presence of colorectal neoplasia. Clinicians could kill two birds with one stone calculating SCORE2. In patients with a high SCORE2, screening colonoscopy aside from cardiovascular risk mitigation could improve outcomes.