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INTRODUCTION: Traditional serrated adenoma (TSA) is a rare yet established precursor to colorectal cancer (CRC). The risk of colorectal neoplasia after TSA removal remains unclear.METHODS: We identified participants without polyps or with TSAs during index colonoscopy from the Mass General Brigham Colonoscopy Cohort (2007-2023). Participants were prospectively followed for recurrence of high-risk polyps and incidence of CRC. We used the time-varying multivariable-adjusted Cox proportional hazards model to estimate the risk of CRC and high-risk polyps associated with baseline diagnosis of TSAs.RESULTS: We identified 109,218 participants without polyps and 252 with TSAs, of whom 35,124 (32%) and 139 (55%) had undergone a follow-up colonoscopy, respectively. TSAs were predominantly located in the distal colon (35%) and rectum (38%), with approximately half sized <10 mm. TSAs tended to demonstrate as a single lesion (84%) but coexist with other types of polyps (70%). Compared with participants without polyps, those with TSAs had higher risk of developing high-risk polyps, high-risk adenomas, high-risk serrated polyps, and CRC, with the hazard ratio (95% confidence interval) of 3.31 (2.35-4.66), 3.07 (2.12-4.44), 6.66 (3.79-11.71), and 7.23 (2.23-23.44), respectively. The risk elevation of high-risk polyps peaked at 3 years post-TSA removal (hazard ratio = 10.85, 95% confidence interval, 6.36-18.52). Among recurrent polyps after TSA removal, 54% (52/96) occurred in the proximal colon and 69% (66/96) was serrated polyps.DISCUSSION: Patients with TSA removal had an elevated risk of colorectal neoplasia, particularly within 3 years after TSA removal, supporting the current US recommendations for a surveillance colonoscopy at 3 years.