Mepact^®(mifamurtide) is the first drug approved for treatment of high-grade resectable non-metastatic osteosarcoma in patients aged 2-30 in the last 20 years. It follows a randomised clinical trial showing a statistically-significant and clinically-relevant decrease in the risk of death without compromising safety. OBJECTIVES: This study assessed the cost-effectiveness and budget impact of mifamurtide added to the standard chemotherapy of cisplatin, doxorubicin and methotrexate with this same standard therapy (ST) without mifamurtide. METHODS: A Markov model was built to combine trial-based outcomes with Spanish resource use and unit cost of compared options. The analysis has been carried out from the perspective of the Spanish National Health Service, with a time horizon of up to 60 years in the base analysis. A probabilistic sensitivity analysis was carried out to assess the influence of the uncertainty of the variables introduced into the model. All the costs are expressed in euros for the year 2011 and, beyond the first year, both costs and effects (quality-adjusted survival) have been discounted with an annual rate of 3%, following local recommendations. RESULTS: The observed greater efficacy of mifamurtide in the trial translates into a gain of 3.03 (undiscounted) and 1.33 (discounted) QALYs and an additional cost of €102,000. The estimated budgetary impact of using mifamurtide in 10% to 100% of the potential population would cost €671,000 and €6.7 million respectively. CONCLUSIONS: The iCER of mifamurtide in Spain is in the low band (< €100,000) of the iCERs obtained by other orphan drugs and would have a limited, predictable and affordable cost in Spain.