OBJECTIVES: A HCV transmission model has been previously developed to describe the dynamics of chronic hepatitis-C (CHC) transmission and progression in the US. In this study, we adapted this model to assess the public health burden of HCV in France. METHODS: This mathematical model captures flows across population compartments based on status of injection-drug use, CHC infection, diagnosis, genotypes, treatment/re-treatment, SVR and disease progression. All input values and predicted values of 2002-2006 from the calibrated model matched closely to published French data. The model was then applied to assess the potential benefits of a hypothetical new CHC regimen (NEW) compared to the current pegylated-interferon/ribavirin (P/R) treatment. Key assumptions in the model included: NEW becomes available in 2011 with 25% incremental SVR rate (70% vs. 45%) from P/R for genotype-1 treatment-naïve patients; 50% SVR rate could be achieved by NEW to re-treat P/R treatment failure patients (TFs); TFs from NEW are not re-treated with NEW; NEW is not used to treat genotype 2/3 patients; P/R durations are consistent with current treatment guidelines by genotypes; diagnosis and treatment rates remain unchanged. RESULTS: Our model projects that, in contrast to P/R projections, the use of hypothetical NEW could cure 32,885 more patients (as defined by the achievement of SVR), and could prevent 7,883 more new cases of CHC, 20,658 more new cases of advanced liver diseases (ALD), and 11,100 more deaths. CHC prevalence in 2040 under NEW is also projected to be lower (29,757 fewer cases), mainly among TFs (16,782) and ALD patients (11,201). CONCLUSIONS: Our model suggests that a novel CHC regimen with higher SVR than the current P/R treatment could potentially have a substantial public health impact in France, mainly due to the associated decrease in the incidence of CHC prevalence, CHC-associated deaths, ALD patients and number of treatment failure patients.