Background: Lynch syndrome (LS) is the most common colorectal cancer (CRC) predisposition syndrome. While patients (pts) with MLH1/MSH2-associated LS are recommended to start colonoscopy between age 20-25, recent guidelines recommend delaying initiation in pts with MSH6/PMS2-associated LS to age 30-35. However, data on findings from colonic surveillance in young MSH6/PMS2-LS pts are limited. Methods: We performed a retrospective review of a multi-institutional cohort of pts with MSH6/PMS2-associated LS who underwent any colonic surveillance prior to age 50, and assessed corresponding pathology results. Neoplastic lesions were defined as a CRC, adenomas, or non-hyperplastic serrated lesions. Clinicopathologic variables were reported with summary statistics and compared using non-parametric tests at the patient level and among pooled procedures. Results: We identified 285 pts [161(56%) MSH6; 124(44%) PMS2] with history of colonic surveillance prior to age 50. 190 (67%) pts were female, with similar sex distribution among the MSH6 and PMS2 groups. 107 (38%) pts had personal history (hx) of any cancer, 67 (42%) MSH6 and 40 (32%) PMS2, including 58 (20%) with CRC [35(22%) MSH6; 23 (19%) PMS2]. Median age at CRC diagnosis (dx) was 39 and did not differ between groups (41 MSH6 vs. 37 PMS2, p = 0.47) with 16 (5.6%) pts dx prior to age 35. 157 (57%) pts had a family hx of CRC, and there was no difference in the rate of CRC between pts with or without family hx of CRC [50%(n = 25) vs 60%(n = 31), p = 0.33]. Pts underwent a median of 2 colonic surveillance procedures (range 1-12) with 824 total procedures, 806 (98%) colonoscopies and 18 (2%) sigmoidoscopies, with 691 (85%) occurring at an academic/tertiary center. Among the 824 pooled procedures, there were 194 (24%) procedures with neoplastic lesions identified, including 19 (2.3%) with advanced adenomas or advanced serrated lesions and 34 (4.1%) with CRC. Among 247 procedures completed at age < 35, 43 (18%) detected neoplastic lesions, including 4 (1.6%) with advanced adenomas or advanced serrated lesions and 9 (3.6%) with CRCs. Notably, in 123 procedures performed prior to LS diagnosis, 43 (35%) had a neoplastic finding with 28 (23%) showing CRC. These findings did not differ between the MSH6 and PMS2 groups. Conclusions: Among this large, multi-institutional cohort of pts with MSH6/PMS2-associated LS with history of colonic surveillance performed prior to age 50, colonic neoplasia was found at similar rates in both MSH6 and PMS2-associated LS. 20% of overall pts had CRC, with 48% presenting prior to LS dx. In surveillance procedures performed < age 35, the upper threshold of initiation of colonic surveillance as per NCCN, 18% found a neoplastic finding with 3.6% finding CRC, highlighting the need to optimize the age of colonic surveillance initiation in MSH6/PMS2-associated LS.