Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in most developed countries. HCV antiviral treatment (peginterferon-a 1 ribavirin) has been shown to be costeffective for patients with no reinfection risk. We examined the cost-effectiveness of providing antiviral treatment for injecting drug users (IDUs) as compared with treating ex/non-IDUs or no treatment. A dynamic model of HCV transmission and disease progression was developed, incorporating: a fixed number of antiviral treatments allocated at the mild HCV stage over 10 years, no retreatment after treatment failure, potential reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%, and 60%). We performed a probabilistic costutility analysis estimating long-term costs and outcomes measured in quality adjusted life years (QALYs) and calculating the incremental cost-effectiveness ratio (ICER) comparing treating IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost-effective option in the 20% and 40% baseline chronic prevalence settings, with ICERs compared with no treatment of Β£521 and Β£2,539 per QALY saved, respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60% baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more cost-effective option (with an ICER compared with no treatment of Β£6,803), and treating IDUs dominated due to high reinfection. A sensitivity analysis indicates these rankings hold even when IDU sustained viral response rates as compared with ex/ non-IDUs are halved. Conclusion: Despite the possibility of reinfection, the model suggests providing antiviral treatment to IDUs is the most cost-effective policy option in chronic prevalence scenarios less than 60%. Further research on how HCV treatment for injectors can be scaled up and its impact on prevalence is warranted. (HEPATOLOGY 2012;55:49-57) C hronic hepatitis C virus (HCV) infection results in over 350,000 deaths per year. 1 In many developed countries, injection drug use is the key HCV transmission risk. 2,3 For example, 90% of infections acquired in the UK are through injections. 4 Treatment and prevention of HCV transmission among injecting drug users (IDUs), therefore, is critical to reducing the burden of liver disease. 2 HCV chronic prevalence within IDU populations varies widely, from below 20% to over 60%. 5 Prevention measures such as opiate substitution therapy and high coverage needle and syringe programs can reduce HCV transmission. 6,7 It is less clear, however, whether current strategies have had a population-level impact. 8,9 Previous mathematical modeling work suggested HCV antiviral treatment could prevent HCV transmission. 10,11 Current HCV antiviral treatment regimens can achieve a sustained viral response (SVR) in 45% (genotype 1) to 80% (genotype 2/3) of infections and economic evaluations suggest treatment is cost-effective for populations with no risk of reinfection. [12][13][14][15]