OBJECTIVES:  To assess the cost-effectiveness of Ruxolitinib versus Best Available Therapy (BAT) for the treatment of Myelofibrosis, from the perspective of the Chilean public healthcare system. METHODS: A Markov cohort state transition model was adapted to represent the natural history of disease, and to estimate the economic and health related quality of life impact. Expected costs were measured in Chilean pesos (1 USD = 654 CLP$) and expected health benefits in quality adjusted life years (QALYs). Health related quality of life was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ-30) and then homologated to generic health states of EuroQol EQ5D through mapping methods. A lifetime time horizon and 3% discount rate was considered for costs and outcomes. A probabilistic sensitivity analyses was performed to account for second order uncertainty. RESULTS: The total expected costs of treating Myelofibrosis with Ruxolitinib are higher than BAT (US$101,926 and US$47,070 respectively). Similarly, the expected incremental health benefit is higher in Ruxolitinib group (0.98 QALYs). The base case scenario (current market prices for all treatments) shows an average ICER of Ruxolitinib versus BAT of US$54,500/QALY. At a suggested threshold between 1xGDP (US$20,000/QALY) and 3xGDP per capita (US$60,000/QALY), the probability of cost-effectiveness of Ruxolitinib was 0% and 73,6% respectively. The ICER is reduced to US$37,875 when the price is reduced a 25% from actual market price. The ICER was most sensitive to the cycle cost of Ruxolitinib and to the mortality hazard ratio. CONCLUSIONS: In an orphan drug context, Ruxolitinib is expected to be cost effective if a small discount is applied to market price.