Opioid use disorder (OUD) is a national crisis that affects public health and economic stability. Recent years have witnessed the highest overdose death toll since 2017, with a 50% increase in overdose mortality rate and limited understanding of underlying contributing factors. Economic disruption from 2020-2022 fundamentally altered employment patterns, healthcare access, and amplified pre-existing economic conditions in communities. Widespread business and school closures persisted through mid-2021 and created substantial unemployment challenges. In response, multiple economic stabilization policies were implemented to offset economic disruption including stimulus payments, child tax credit, more generous unemployment and food assistance, and eviction moratoria. Healthcare policies such as continuous Medicaid coverage and medication for OUD (MOUD) policies aimed to increase access to care and treatment. While economic and social disruption can influence OUD trajectories, it remains unclear which components of these policy responses and resulting economic and healthcare changes differentially affected individuals with existing or elevated risk of OUD. Additionally, the uneven distribution of impacts across communities requires further investigation. The goal of this study is to leverage comprehensive claims and electronic health data, capturing nearly half of the U.S. population from 2018 through 2025, to test our hypothesis that economic and employment disruption escalate the prevalence of OUD and related adverse outcomes. We further hypothesize that policies enacted in recent years (e.g., take-home methadone, telemedicine buprenorphine, the MAT Act, continuous Medicaid) increased access to treatment and reduced related harms. Building on our extensive existing work, we use quasi-experimental methods to measure adverse OUD-related outcomes using existing records capturing longitudinal OUD at the individual patient and community levels. In Aim 1, we evaluate whether the increase in OUD mortality during 2020 was worse in communities with higher pre-existing opioid-related challenges or greater employment disruption. In Aim 2, we evaluate longer-run OUD trajectories for communities that experienced greater degrees of economic loss and differing degrees of policy response over five years. We further examine OUD outcomes and leverage individual longitudinal data for important subpopulations (e.g., adolescents, older adults). At the successful completion of the proposed research, the expected outcomes are evidence-based insights into economic, clinical, and policy factors that influenced OUD diagnoses, treatment initiation and adherence, healthcare utilization, and mortality outcomes. This research will support NIH NIDA's goals by identifying economic and clinical factors that impact OUD and populations experiencing barriers to care access.