OBJECTIVES: Ipilimumab was the first compound to substantially prolong survival in advanced melanoma. Evaluate the cost-effectiveness of ipilimumab in untreated advanced melanoma compared to dacarbazine and vemurafenib from a Swedish national payer perspective (TLV/NLT). METHODS: A three-state Markov model with stable disease, progression and death was developed, estimating costs and benefits over a lifetime horizon. Given a lack of head-to-head data and a connected evidence network to allow for a robust NMA, the comparison used two sources of data unadjusted for study characteristics. Ipilimumab survival data were based on a pooled sample of treatment-naïve patients from clinical trials (n=78) and real-world settings (n=181), the clinical data package used for EMA submission. Parametric extrapolation methods were applied to dacarbazine data from CA184-024. Mixture modelling was used to extrapolate vemurafenib data from BRIM-III. Resource use was taken from a survey of Swedish oncologists (n=5). EORTC-8D utility data from an untreated population were used because they match the population of interest. Costs were obtained from official Swedish price lists. Survival and utility assumptions were varied in scenario analyses. RESULTS: Ipilimumab was associated with a 0.93 QALY gain and an ICER of SEK782,000 (€84,000) versus dacarbazine. Ipilimumab dominated vemurafenib with a 0.76 QALY gain and a SEK109,000 (€15,000) cost-saving. The unadjusted comparison was the most conservative among alternative methods of clinical comparisons explored. The ICER versus dacarbazine was SEK521,000 (€56,000) using a published survival algorithm (7) and SEK532,000 (€57,000) using a covariate-adjusted survival regression based on the 78-patient dataset. A real-world scenario using the patient shares of dacarbazine and vemurafenib was also deemed cost-effective. CONCLUSIONS: As in the previously treated setting, ipilimumab produces large (>0.5 year) survival and quality-adjusted survival gains relative to current treatments.TLV/ NLT considered ipilimumab a cost-effective treatment for advanced melanoma based on these results.