OBJECTIVES: A relevant proportion of patients affected by Chronic Hepatitis C(CHC) is older than 65 years. These patients have been undertreated in the past two decades, due to poor eligibility to interferon-containing regimens. New all-oral, interferon-free antivirals may represent a valuable option for this population. Our aim was to assess the cost-effectiveness of sofosbuvir plus ledipasvir(SOF/LDV) therapy in genotype 1(G1) and 4(G4) CHC elderly patients. METHODS: A Markov model of CHC natural history was built. The model focuses on CHC patients older than 65 years and assessed the impact of liver fibrosis (METAVIR F3 and F4), age and frailty phenotype, defined by Fried’s (not frail, pre-frail and frail), on the cost-effectiveness of SOF/LDV versus no treatment. The model estimated costs, Life Years and Quality-Adjusted Life Years (QALY) using the lifetime time horizon and the National Health System perspective. Results were presented as incremental cost-effectiveness ratios (ICERs) per QALY gained. RESULTS: The cost-effectiveness of all-oral and IFN-free treatment regimen in HCV elderly patients is influenced by all three parameters assessed in our simulation. ICER was higher in lower fibrosis stages and increased with age and frailty phenotype. In F3 and F4 patients ICER was below 40,000 €/QALY up to age 83.3 and over 85 years in non-frail patients, up to age 79.5 and 82.5 in pre-frail and  up to age 76.5 and 79.5 in frail, respectively. The ICER was more sensitive to drug price and SVR probability. Further, the mortality rate not-liver related had a higher impact in the not-frail patients. CONCLUSIONS: Age and fibrosis stage are not enough to assess the cost-effectiveness of anti-HCV treatment in elderly subjects. A careful assessment of the patient geriatric status should be mandatory, especially in patients older than 75 years, to better allocate the resources available and to prioritize the access to the treatment.