OBJECTIVES:  Chronic hepatitis C (CHC) with an estimated global prevalence of 3% (1.9% in Greece), poses an important disease and economic burden on healthcare systems internationally. Ledipasvir/Sofosbuvir (LDV/SOF), is the first fixed-dose combination of antiviral agents approved for CHC. In view of the clinical efficacy data for LDV/SOF, the objective of this study was to perform a cost-effectiveness analysis of LDV/SOF versus available comparators for the treatment of genotype 1 CHC patients in Greece. METHODS:  A Markov state-transition model was used in order to evaluate the lifetime health and economic outcomes of genotype 1 CHC patients over lifetime depending on initial treatment choice. The model considered cohorts of either treatment-naïve (TN) or treatment-experienced (TE) patients, with subgroup analyses conducted for cirrhotic and non-cirrhotic subjects. The model was populated with clinical effectiveness data from the literature and Greek-specific data on health resource use and costs. A third party-payer perspective was adopted and costs and outcomes were discounted at 3%. RESULTS:  In TN non-cirrhotic patients LDV/SOF was dominant versus Simeprevir+SOF; Ombitasvir/paritaprevir/ritonavir+dasabuvir(+ribavirin); SOF+peginterferon+ribavirin; SOF+ribavirin and cost-effective (ICERs ranging from €5,134/QALY to €11,454/QALY) versus peginterferon+ribavirin; simeprevir+peginterferon+ribavirin and no treatment. Considering TN cirrhotics LDV/SOF was dominant versus SOF+peginterferon+ribavirin; SOF+ribavirin; SOF+daclatasvir; Simeprevir+SOF and cost-effective versus simeprevir+peginterferon+ribavirin; peginterferon+ribavirin and no treatment (ICERs ranging from €3,948/QALY to €4,481/QALY). The according results for TE patients suggested dominance of LDV/SOF versus SOF+peginterferon+ribavirin; SOF+daclatasvir for cirrhotic subjects and cost-effective ICERs versus simeprevir+peginterferon+ribavirin; peginterferon+ribavirin; Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin and no treatment (ICERs: €3,447/QALY; €4,156/QALY; €14,094/QALY and €4,478/QALY accordingly); while for non-cirrhotics LDV/SOF dominated SOF+peginterferon+ribavirin; Simeprevir+SOF and was cost-effective compared to peginterferon+ribavirin; simeprevir+peginterferon+ribavirin; and no treatment (respective ICERs: €13,966/QALY; €14,930/QALY; €13,302/QALY). Cost/pack and discounting rates were the most influencing factors of the ICER. Results were robust to probabilistic analysis. CONCLUSIONS:  LDV/SOF appears to yield favorable health and economic outcomes compared to current treatment options in the setting of Greece.