This US study examines trends and factors associated with buprenorphine misuse among persons with or without an opioid use disorder (OUD) from 2015-2019. The prevalence of buprenorphine misuse in persons with an OUD trended downward during the study period; in 2019 alone, nearly 75% of adults did not misuse their prescribed buprenorphine. Both OUD and buprenorphine misuse were associated with suicide risk, emphasizing the importance of timely interventions. The study’s findings underscore expansion of treatment access, strategy development to monitor and reduce buprenorphine misuse, and addressing conditions associated with misuse. Better understanding can also inform policy toward clinical practice development, education, and training initiatives.