OBJECTIVES:  To evaluate the cost-utility of pirfenidone for the treatment of patients with mild to moderate IPF in comparison to best supportive care and nintedanib, from the Italian NHS perspective. METHODS:  A Markov decision model with 3-month cycles and a lifetime horizon was adopted. There are four health-states in the model (progression-free, progressed, lung-transplant and death). Clinical data, utilities and transitions were based on clinical trials, systematic review and meta-analysis of IPF treatments. Treatment costs were considered (drugs, disease management, hospitalization, lung transplant and end of life). Drug acquisition costs were derived from the ex-factory price. Disease management costs (continuous treatment and monitoring of disease progression) were applied to all patients in progression-free and progressed health states. Hospitalisations were considered in the model to account for serious adverse events associated with treatment, exacerbations and natural course of disease. Lung transplant costs were applied as a one-off cost to all new patients entering the lung transplant state. A one-off end of life cost (home care and hospital) was applied to patients who died due to IPF-related causes. Italian costs were obtained from literature and local sources (National Tariffs). Costs and health outcomes were discounted at an annual rate of 3%. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. RESULTS:  Pirfenidone increased life years (LYs) and QALYs compared to nintedanib (+1.30 LYs; +1.04 QALYs) and BSC (+2.42 LYs; +1.95 QALYs). The total cost was €102,504 with pirfenidone, €93.948 with nintedanib and €26,570 with BSC. The incremental cost-effectiveness ratio (ICER) of pirfenidone was €6,460/LY and €8,199/QALY versus nintedanib and €31,360/LY and €39,012/QALY versus BSC. Deterministic and probabilistic sensitivity analyses confirmed base case results. CONCLUSIONS:  According to this analysis, in Italy pirfenidone can be considered as a cost-effective strategy compared to BSC or nintedanib for the treatment of mild to moderate IPF.