OBJECTIVES: To assess the cost-utility of first-line nilotinib vs imatinib in patients with chronic myeloid leukaemia (CML) eligible to start the treatment-free remission (TFR) phase in the Italian healthcare setting (NHS). METHODS: A previous cost-utility model, simulating a cohort of 20,000 patients individually followed, was adapted to the Italian NHS. CML patients could start treatment with nilotinib or imatinib while for both arms a second-line with nilotinb is expected according to the Italian clinical practice. Patients remaining on first-line at thirty-six months and with a BCR-ABL score less than MR4.5 are considered long-term responders and may enter the treatment free remission (TFR) phase. Model outcomes are expressed in Quality-Adjusted-Life-Years (QALYs) and life-years-gained (LYG). Clinical data were derived from ENEST-nd trial. A panel of experts in CML treatment provided input on healthcare resource consumption: routine visits, laboratory/instrumental tests, adverse events management and drug consumption. Costs - Euros (€) 2015 - were quantified using Hospital National Tariffs and ex-factory drug prices. The model assumes that generic imatinib and nilotib become available as of January 2017 and July 2023,respectively, and therefore a 74% price discount for both drugs was included.  Costs and outcomes were discounted at 3% according to Italian Guidelines for Economic Evaluations. Incremental cost-effectiveness ratios (ICERs) were calculated to estimate the incremental cost of a TFR patient with nilotinib. RESULTS: An incremental number of 3,773 patients are eligible to TFR with nilotinib vs imatinib with €33,748 total costs/patient. An improvement of +1.06 QALYs and +1.49 LYG is also observed in the nilotinib arm. The ICERs for nilotinib vs imatinib are €39,935/QALY and €31,969/LYG. CONCLUSIONS: The model shows that a greater number of patients enter TFR with nilotinib with acceptable ICERs vs imatinib.