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Background Pragmatic colorectal cancer (CRC) screening trials compare colonoscopy with faecal immunochemical testing (FIT), but differences in adherence complicate interpretation of comparative outcomes.Objective To compare 10-year risks of CRC mortality, CRC incidence and all-cause mortality under one-time colonoscopy versus sustained FIT strategies in the COLONPREV Trial.Design We conducted a post hoc per-protocol analysis of 17 270 screening initiators aged 50–69 years in eight Spanish regions, using inverse probability weighting to adjust for observed confounding and informative protocol deviations.Results Weighted 10-year risks were similar for CRC incidence (0.80% FIT vs 0.86% colonoscopy; risk difference (RD) 0.06%, 95% CI −0.25% to 0.37%) and all-cause mortality (4.02% vs 4.09%; RD 0.07%, 95% CI −0.76% to 0.84%). CRC mortality was lower with colonoscopy (0.072% FIT vs 0.042% colonoscopy; RD −0.03%, 95% CI −0.12% to 0.06%), but estimates were imprecise.Conclusion Sustained colonoscopy and FIT showed similar 10-year outcomes overall, highlighting the importance of adherence pathways in pragmatic screening trials.Trial registration number ClinicalTrials.gov: NCT00906997.