Situated within clinical practice, pragmatic trials aim to measure the effectiveness or feasibility of a treatment in the “real world.” However, in substance use treatment and research, the “real world” is characterized by contentious drug policies, politics, and public perceptions that vary by jurisdiction. While such contextual influences typically go unmeasured in clinical research, there are wide-ranging, place-based features that can shape participants’ clinical trial experiences and substance use outcomes. To understand how research processes are embedded in complex contexts, I conducted a nested qualitative study with 75 participants in a multi-site, pragmatic RCT testing models of care for opioid use disorder across five Canadian cities. In this presentation, I describe how localized differences related to place (e.g., study spaces), policy (e.g., insurance coverage) and healthcare contexts (e.g., treatment availability) structure participants’ trial enrollment, medication access, and medication adherence. These results highlight how fundamental differences in contextualized social dynamics, health policies, and local politics have implications for the comparative analysis of study data in multisite pragmatic trials and for the conduct of research with marginalized populations.