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Background: The advent of direct-acting antiviral (DAA) medications has facilitated opportunities to treat hepatitis C virus (HCV) among people who inject drugs (PWID). However, there remains a need for data about how to optimally support PWID throughout DAA post-treatment trajectories, including with regard to re-infection prevention. The objective of this study is therefore to identify how PWID with lived experience of HCV describe their expectations and experiences related to health and social outcomes, contexts, and substance use practices following completion of DAA treatment., Methods: We thematically analyzed data from in-depth, semi-structured interviews, conducted between January and June 2018, in Vancouver, Canada, with a purposive sample (n = 50) of PWID at various stages of DAA treatment (e.g., pre, peri, post)., Results: Our analysis yielded three themes. First, while participants had hoped to experience holistic enhancements in wellbeing following HCV cure, discussions of actual post-treatment experiences tended to be located in physical health (e.g., increased energy). Second, participants often pointed to the ways in which HCV-related and other stigmas had restricted opportunities for health and healthcare access. Participants therefore identified stigma-reduction as a key motivator of HCV cure, and while reductions in internalized stigma were sometimes achieved, participants underscored that other forms of enacted stigma (e.g., related to: substance use, HIV, poverty) had continued to feature prominently in their post-treatment lives. Third, participants described considerable knowledge about how to prevent HCV re-infection following cure, but they also expressed apprehensiveness about how socio-structural barriers, including stigma and criminalization, could interfere with harm reduction and re-infection prevention efforts., Conclusions: DAAs are transforming the health and wellbeing of some PWID. Yet, HCV-related policy must extend beyond the scale-up of DAAs to include concerted public health investments, including anti-stigma efforts and improvements to the social welfare system, to meaningfully advance equity in PWID's post-treatment trajectories and outcomes., Competing Interests: Declarations of Interest None., (Copyright © 2021 Elsevier B.V. All rights reserved.)