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Injecting risk behaviours among people who inject drugs (PWID) and high-risk sexual practices among men who have sex with men (MSM) are important routes of hepatitis C virus (HCV) transmission. Current direct-acting antiviral treatment offers unique opportunities for reductions in HCV-related liver disease burden and epidemic control in high-risk groups, but these prospects could be counteracted by HCV reinfection due to on-going risk behaviours after successful treatment. Based on existing data from small and heterogeneous studies of interferon-based treatment, the incidence of reinfection after sustained virological response range from 2-6/100 person years among PWID to 10-15/100 person years among human immunodeficiency virus-infected MSM. These differences mainly reflect heterogeneity in study populations with regards to risk behaviours, but also reflect variations in study designs and applied virological methods. Increasing levels of reinfection are to be expected as we enter the interferon-free treatment era. Individual- and population-level efforts to address and prevent reinfection should therefore be undertaken when providing HCV care for people with on-going risk behaviour. Constructive strategies include acknowledgement, education and counselling, harm reduction optimization, scaled-up treatment including treatment of injecting networks, post-treatment screening, and rapid retreatment of reinfections.