Project Summary/Abstract The United States continues to be faced with an ongoing public health crisis of drug overdose and other drug- related harms. In 2020 there were more than 100,000 overdose deaths, with more than half due to synthetic opioids such as fentanyl. Despite significant public health attention toward the opioid crisis in the US, these harms continue to grow and to have tremendous impacts on individuals, families and communities. Among the challenges in addressing the opioid crisis is that it continues to evolve, with changes in the drug supply, available treatment, the populations affected, and public perceptions. Long-term data on the course of opioid use disorder (OUD), individual differences in prognosis, the long-term effects of treatment, and markers of recovery are urgently needed to inform public health interventions, treatment implementation, and novel treatment development. The overarching objective of this project is to conduct a long-term follow-up of two large National Institutes on Drug Addition (NIDA) Clinical Trial Network (CTN) clinical trials funded through the National Institutes of Health (NIH) Helping End Addiction Long-term (HEAL) Initiative to begin to fill these important gaps in knowledge. This protocol focuses on the first stage, a longitudinal follow-up study that will collect yearly outcomes data for an initial 4-year study period on adults with opioid use disorder (OUD). This longitudinal, observational study will entail annual phone assessments of domains of interest (e.g., substance use, treatment engagement) as well as monthly assessments that are distributed via SMS and email to be completed electronically by the participant. This first stage aims to characterize the long-term course of OUD and to create a repository of outcomes data that will be used for future concept development and analysis of studies within the CTN that evaluate the long-term course and recovery of OUD. In the second stage, the study aims to expand data collection to additional populations of interest, including from other CTN studies.