OBJECTIVES: The goal of hepatitis C virus (HCV) treatment is the attainment of sustained virologic response (SVR). As the predominant source of infection in the UK is associated with high-risk behaviour among people who inject drugs (PWID), reducing the infected population via treatment may prevent future infections. This study evaluated the health economic impact of two treatment regimens, daclatasvir+sofosbuvir (DCV+SOF) and telaprevir+pegylated interferon-alfa+ribavirin (TVR+PR), in a cohort of people with high transmission risk, when accounting for future infections avoided. METHODS: A combined dynamic HCV transmission and published disease progression model (MONARCH) was populated with published UK data for PWID. Future costs, life years and quality-adjusted life-years (QALYs) were discounted at 3.5%. A prevalence parameter amongst PWID of 25% was utilised and results presented per 1,000 patients. The impact of treating all (25/1000) or a proportion (8/1000) of patients with DCV+SOF or TVR+PR within a one-year period was evaluated. Published SVR rates of 95% and 59% were applied to DCV+SOF and TVR+PR, respectively. RESULTS: Ignoring future infections, DCV+SOF was associated with incremental per-patient costs of +£18,166 and incremental benefits of +1.4 QALYs and an incremental cost-effectiveness ratio (ICER) of £9,867 compared to TVR+PR. When considering reduced transmission, additional per-patient discounted cost savings of £8,803 and QALY gains of 1.42 were estimated, from 1,845 future infections and 328 related long-term complications avoided over the period 2015–2065 if all patients were treated. The associated ICER decreased from £9,867 to £2,869. Assuming 8/1000 PWID were treated, the ICER decreased from £9,867 to £8,156. CONCLUSIONS: Accounting for the impact of SVR on future disease transmission can significantly impact cost-effectiveness results in HCV. Factoring in the consequences of infections avoided is imperative when evaluating the cost-effectiveness of HCV treatment among groups at high risk of transmission, such as PWID.