e18259 Background: NCI instituted a Central IRB (CIRB) with voluntary participation in 2001 for its late-phase trials and demonstrated that efficiency could be improved and costs reduced (Wagner et al JCO, 2010; 28). As a forerunner to the new NIH policy for single IRBs for all NIH multi-site trials (Hudson et al. JAMA Oct 4, 2010), NCI implemented a new CIRB model in 2014 where the CIRB was the IRB of record. We report adoption data of the new model within NCI’s National Clinical Trials Network (NCTN) and lessons learned from the rollout. Methods: We reviewed: Annual CIRB participant data from 2013-2016; site/accrual data for late phase trials activated between 2013-2016 (N = 64) via CIRB or local IRBs; and data from CIRB reports to identify acceptance and lessons learned. We compared time required for CIRB protocol reviews via the new model to baseline measures in the literature. Results: Of the 2,300 U.S. NCTN sites, the percentage of participation went from 47% in 2013, to 74% (2014), 79% (2015), and 81% (2016). For activated trials, a median of 43% of sites used their local IRB in 2013, dropping to 18% in 2014, 5% in 2015, and only 1% in 2016; i.e., 99% of sites opening trials in 2016 did so using the CIRB. Annual accrual to NCTN trials remained steady through the CIRB adoption; CIRB sites represented a median of 56% of total accrual in 2013 increasing to 87% in 2016. Help-desk and survey data indicate increased acceptance and a reduction of concerns over the 3 years. Previous analyses prior to 2013 reported a median of 70-123 days required from protocol application receipt to final CIRB approval; the new model reports a median of 41 days in 2016. Conclusions: NCI has demonstrated that a single IRB for multi-site trials is not only viable but valuable. Its new CIRB model rollout over 3 years has resulted in a doubling of site adoption, high utilization rates, further efficiencies, and overall acceptance, with no noticeable effect on overall NCTN accrual. Our experiences provide important lessons learned and insights into the successful implementation of a single IRB at a national level, and support the feasibility of NIH’s recently finalized policy requiring all sites to use a single IRB for multi-site research.