Project Summary/Abstract More than 70% of the 2.1 million people with opioid use disorder (OUD) in the United States do not receive evidence-based medication-assisted treatment (MAT), and it remains a challenge for health systems to identify and implement effective system and policy interventions to close the treatment gap. Our long-term goal is to inform the design of optimal policies to improve OUD treatment within healthcare systems. The overall objective of the proposed research is to determine where and how such interventions should be targeted along the OUD care cascade to achieve maximum impact in closing the treatment gap, using the Veterans Health Administration (VHA) as an example. The rationale for this project is that insights gained from studying the dynamics of OUD treatment within the VHA will also have broad theoretical and practical applicability to other large delivery systems. To accomplish the overall objective, the proposed research aims to: (1) Estimate the impacts of policy interventions to improve OUD treatment; and (2) Model combinations of policies to achieve population-level treatment targets. Under the first aim, we will simulate the effects of individual policies that seek to engage patients in treatment, initiate them onto MAT, and/or increase treatment retention. We will vary the parameters of a calibrated compartmental model of OUD diagnosis and treatment to quantify impacts of implementing different policies. For the second aim, we will model combinations of policies to simultaneously address treatment engagement, MAT initiation, and retention in order to examine synergies and/or redundancies in policy effects. We will identify the necessary levels of increase in treatment initiation, retention, and delivery capacity to achieve targets in overall mortality reductions and proportion of OUD population treated. The research proposed in this application is innovative because it incorporates real-world delivery constraints and utilizes a novel and rich dataset drawn from VHA’s electronic health record. The research proposed is significant because it will provide actionable insights that decision makers can use to address the substantial health and financial toll of the opioid epidemic, by prioritizing development and implementation of effective interventions along the OUD care cascade. This proposal responds to AHRQ’s Special Emphasis Notice (NOT-HS-18-015) which calls for health services research to improve opioid abuse treatment and recovery by providing “evidence-based guidance to policy makers about the effects of new policies” to address the crisis.