Health insurance improves health and reduces mortality. Expanding insurance is a central feature of the Affordable Care Act (ACA). Persons who use drugs (PWUDs) have historically been at high risk of being uninsured. It is unknown if Appalachian PWUDs, who live in an extremely economically distressed region, are more likely to be insured since implementation of the ACA. Data from a cohort of 503 PWUDs from eastern Appalachian Kentucky, who were interviewed at seven time-points between 2008 and 2017, were analysed using mixed effects regression models.