OBJECTIVES To assess the cost-effectiveness of ipilimumab compared to dacarbazine as first-line treatment in patients with advanced metastatic melanoma. METHODS A three-state Markov (progression-free, progression and death) with three-week cycles model using the Spanish Healthcare System perspective was developed over a lifetime horizon. The clinical profile of ipilimumab (3 mg/kg) was obtained from a pooled dataset of chemotherapy naive patients from four phase II and phase III studies, and from the CA184-024 trial for dacarbazine. Parametric extrapolation methods were used to project survival over lifetime. Costs included were: drug acquisition (ex-factory price -7,5% mandatory rebate) and administration, medical/terminal care, and adverse events management. Unit costs were derived from Spanish healthcare cost databases (Euros, 2013). For drugs with a double-pricing system (like ipilimumab), costs were based upon the official notified prices in Spain. Costs and benefits were discounted at 3%. Utility values were taken from the CA184-024 trial. Univariate and probabilistic sensitivity analyses (PSA) were performed. RESULTS The life years (LYs) and quality-adjusted life years (QALYs) gained with ipilimumab as first-line treatment over dacarbazine were 2.01 and 1.68, respectively. The incremental cost of using ipilimumab versus dacarbazine was 69,598 €. The incremental cost-effectiveness ratio (ICER) and the incremental cost-utility ratio (ICUR) were 34,566€/LY gained and 41,459€/QALY, respectively. PSA showed that ipilimumab is up to 100% and 90% likely to be cost-effective at the threshold established by the NICE for oncology drugs that meet ‘End-of-Life’ criteria (50,000-62,000€) for ICER and ICUR, respectively. Additionally, at the threshold acceptable in Spain (30,000-45,000€) the likelihood of ipilimumab being cost-effective is up to 94% and 66% for ICER and ICUR, respectively.  CONCLUSIONS Results suggest that ipilimumab is a cost-effective alternative for previously untreated patients with advanced metastatic melanoma in Spain.