OBJECTIVES: Genetically-targeted therapies are both promising and costly advances in the field of oncology. This study aims to evaluate the cost-effectiveness of vemurafenib versus ipilimumab as first-line treatments in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma from a Spanish healthcare system perspective. METHODS: We performed a cost-effectiveness analysis to compare both strategies for patients with BRAF positive metastatic melanoma using a probabilistic model. Since head-to-head trials are not available, overall (complete and partial) response rates were obtained from the phase III randomized-controlled trials of vemurafenib (57.0%; 95% CI 51.6-65.2%) and ipilimumab (15.2%; 95% CI 12.2-18.2%). The cost of treatment regimens was calculated using the recommended dose schedules as per the Summary of Product Characteristics. The treatment duration with vemurafenib was 6.9 months (median progression-free survival). Four doses of ipilimumab were considered. The prices used in the analysis correspond to those currently approved in Spain (in EUR, 2015).Monte-Carlo simulation was chosen as it allows simulating the effect of changes in different parameters obtained from clinical studies and other sources to describe real-life distributions. Parameters used in the simulation were the progression free survival, body weight and overall response rates. Additional threshold sensitivity analyses for possible ipilimumab price discounts were performed. RESULTS: