PROJECT ABSTRACT In the ongoing public health crisis of opioid overdoses, the incidence of opioid use disorder (OUD) has increased and medication-based treatment for OUD remain underutilized. While longer OUD treatment duration is generally associated with improved patient outcomes, maintaining continuous health insurance coverage represents a significant challenge to sustaining access to treatment. Patients with OUD may be vulnerable to experiencing health insurance instability that results in barriers to OUD treatment access. High- risk care transitions or disruptions to treatment may increase risk of relapse, overdose, and mortality. Despite the potential for insurance instability to create significant barriers to OUD treatment continuity, current knowledge regarding its health and mortality impacts is limited due to the challenge of capturing and evaluating patient outcomes after disenrollment from health systems. To address this knowledge gap, the proposed Clinical Trials Network (CTN) research concept seeks to examine the association of health insurance instability and mortality risk among patients receiving buprenorphine treatment for OUD in a multi-site cohort study, leveraging data from the Prescription Opioid Registry (POR) that include four diverse health systems participating in the CTN Health Systems Node. The aims of the study are: (1) Ascertain fact and cause of death from the National Death Index; (2) Examine insurance instability during buprenorphine treatment for OUD and associated patient and health plan factors; (3) Assess the association of insurance instability and risk of all-cause, opioid overdose, and other substance-related overdose mortality; and (4) Link data from one study site to all-payer claims data and criminal justice data to explore events associated with disenrollment from health plans. The proposed research concept will contribute to understanding the mortality consequences associated with insurance instability for patients in treatment for OUD. It will also inform strategies in health systems to ensure continuity of treatment access and to prevent poor outcomes in patients at risk of experiencing insurance coverage disruptions.