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While regulatory frameworks governing methadone maintenance therapy (MMT) require highly regimented treatment programs that shape treatment outcomes, little research has examined the effects of regulatory changes to these programs on those receiving treatment, and located their experiences within the wider context of social-structural inequities. In British Columbia (BC), Canada, provincial regulations governing MMT have recently been modified, including: replacing the existing methadone formulation with Methadose(®) (pre-mixed and 10 times more concentrated); prohibiting pharmacy delivery of methadone; and, prohibiting pharmacies incentives for methadone dispensation. We undertook this study to examine the impacts of these changes on a structurally vulnerable population enrolled in MMT in Vancouver, BC. Qualitative interviews were conducted with 34 people enrolled in MMT and recruited from two ongoing observational prospective cohort studies comprised of drug-using individuals in the six-month period in 2014 following these regulatory changes. Interview transcripts were analysed thematically, and by drawing on the concept of 'structural vulnerability'. Findings underscore how these regulatory changes disrupted treatment engagement, producing considerable health and social harms. The introduction of Methadose(®) precipitated increased withdrawal symptoms. The discontinuation of pharmacy delivery services led to interruptions in MMT and co-dispensed HIV medications due to constraints stemming from their structural vulnerability (e.g., poverty, homelessness). Meanwhile, the loss of pharmacy incentives limited access to material supports utilized by participants to overcome barriers to MMT, while diminishing their capacity to assert some degree of agency in negotiating dispensation arrangements with pharmacies. Collectively, these changes functioned to compromise MMT engagement and increased structural vulnerability to harm, including re-initiation of injection drug use and participation in high-risk income-generating strategies. Greater attention to the impacts of social-structural inequities on MMT engagement is needed when modifying MMT programs, especially as other jurisdictions are adopting similar changes. Comprehensive environmental supports should be provided to minimize adverse outcomes during transitional periods., (Copyright © 2015 Elsevier Ltd. All rights reserved.)