OBJECTIVES Chronic hepatitis C (CHC) is a major public health problem contributing to more than 86,000 premature deaths in Europe. Pegylated interferon-α plus ribavirin (PR) based therapy, including regimens with boceprevir (BOC) or telaprevir (TVR) in HCV genotype-1 patients, have failed to provide more extensive therapeutic benefit leaving space for substantial outcomes improvement. Sofosbuvir (SOF) – a pan-genotypic RNA polymerase inhibitor – has shown unprecedented sustained virologic response rates and tolerability profiles. The objective of this study was to estimate SOF contribution to public health by exhausting CHC therapeutic efficiency. METHODS Therapeutic efficiency was defined as maximum capacity to benefit from treatment in terms of life years (LY) relative to the general population’s life expectancy. The natural history of CHC and treatment implication was modelled with a discrete-time Markov allowing for long term assessment in terms of HCV genotype, fibrosis progression, HIV co-infection status and previous treatment experience. Treatment options compared were dependent on interferon eligibility/tolerance and genotype: PR, SOF/PR, BOC/PR and TVR/PR in elegible/tolerant patients (BOC/TRV regimens in genotype-1 only; SOF/ribavirin in genotype-2). For ineligible/intolerant patients, comparison of SOF/ribavirin was performed against lack-of-therapy. RESULTS In mono-infected HCV genotype-1 patients SOF/PR treatment is estimated to result in 4.3 LY, 7.0 LY or 8.0 LY gained in comparison to TRV/PR, BOC/PR or PR, respectively. In genotype-1 and genotype-2 HIV-coinfected patients elegible for interferon treatment, the estimated LY gained with SOF treatment is 11.8yrs and 5.0yrs, respectively. In patients ineligible for interferon treatment, SOF is expected to almost double life expectancy irrespective of the genotype, with therapeutic efficiency ranging from 79% to 95%. In co-infected patients, therapeutic efficiency of SOF is expected to range between 84.3% and 92.4% of general population life expectancy. CONCLUSIONS Sofosbuvir-containing regimens are expected to maximize years of life lived and maximize efficiency relative CHC patients residual life expectancy.