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Introduction Post-colonoscopy colorectal cancers (PCCRCs) are thought to have a significant contribution from proximal serrated lesions as precursors that are difficult to detect. We assessed the effectiveness of chromocolonoscopy powered for detection of proximal significant serrated lesions.Methods Open-label, multicentre, RCT including patients invited to index bowel cancer screening colonoscopies from 18 centres in England and Wales (ISRCTN: 98539180) randomly assigned to either high definition white light colonoscopy (HDWL) or HDWL + chromocolonoscopy with indigo carmine dye 0·2%.(HDCC). Colonoscopy and pathology data from index and associated clearance procedures over the next 12 months were analysed.Results Between Jun 23, 2021, and Feb 7, 2024, 2720 patients were randomised (HDWL: n=1363; HDCC: n=1357). After controlling the family-wise error rate at α = 0.05 using the Holm–Bonferroni method, detection was significantly higher with HDCC for the outcomes in table 1.Conclusions Although it did not significantly increase detection of proximal significant serrated lesions, chromocolonoscopy significantly increases the detection of all polyps, serrated polyps, and advanced adenomas in both the whole and proximal colon and the mean number of advanced neoplasia in the whole colon. We await the longer term follow up of these patients in stage 2 of the trial to investigate whether or not these differences are clinically meaningful.There was no significant difference in the proportion of patients with proximal significant serrated lesions (35/1363(2.6%) with HDWL vs 41/1357 (3.0%) with HDCC; OR=1.18 (95%CI: 0.75-1.87); p=0.478).Abstract O84 Table 1Significant outcomesOutcomeHDWLHDCCTreatment effectmean number of polyps per patient2.012.64IRR=1.32 (95%CI: 1.26-1.39), p<0.001mean number of polyps in the proximal colon per patient1.001.48IRR=1.49 (95%CI: 1.39-1.60), p<0.001proportion of patients with polyps found in proximal colon553/1363 (40.6%)704/1357 (51.9%)OR=1.61 (95%CI: 1.38-1.88), p<0.001mean number of serrated lesions per patient found anywhere0.460.64IRR=1.39 (95%CI: 1.26-1.55), p<0.001mean number of serrated lesions per patient found in proximal colon0.200.33IRR= 1.64 (95%CI: 1.41-1.91), p<0.001proportion of patients with serrated lesions found in proximal colon172/1363 (12.6%)262/1357 (19.3%)OR= 1.69 (95%CI: 1.36-2.09), p<0.001mean number of advanced neoplastic lesions per patient found anywhere0.400.50IRR=1.25 (95%CI: 1.12-1.40), p<0.001mean number of advanced adenomas per patient found anywhere0.350.44IRR=1.26 (95%CI: 1.12-1.42), p<0.001mean number of advanced adenomas per patient in proximal colon0.070.10IRR=1.50 (95%CI: 1.15-1.94), p<0.001proportion of patients qualifying as high risk surveillance366/1363 (26.9%)440/1357 (32.4%)OR=1.32 (95%CI: 1.12-1.56), p=0.001)