OBJECTIVES: To evaluate the cost-effectiveness, from an Australian health system perspective, of nivolumab versus ipilimumab for treatment of patients with previously-untreated, BRAF wild-type (WT) advanced melanoma (AM), comprising unresectable and/or metastatic melanoma).  METHODS: A state-transition Markov model with 3 health states (‘Alive, pre-progression’, ‘Alive, post progression’ and ‘Dead’) and 12-week cycles was constructed to simulate the history of BRAF-WT Australian patients with AM.  A 5% annual discount rate was applied to costs and health measures. A 10-year time horizon was selected to capture the long-term survival achieved with immunotherapy agents.  For the Nivolumab Group, risks of progression and death were based on those observed in the Nivolumab arm of study CA209-066 (nivolumab versus dacarbazine). Log-logistic functions were used to extrapolate trial data up to 10 years based on AIC and clinical plausibility.  For the Ipilimumab Group, transition probabilities were derived from applying hazard ratios (HRs) to the corresponding transition probabilities in the Nivolumab Group. In the absence of head-to-head evidence, HRs were calculated by indirect comparison of nivolumab versus ipilimumab using published data. AM management costs were estimated by survey of Australian clinicians. Ipilimumab costs were based on prices reimbursed under the Pharmaceutical Benefits Scheme (PBS) of Australia.Nivolumab costs were based on the expected reimbursed price under the PBS per course of treatment. Utilities were determined using EQ-5D data from study CA209-066. Probabilistic sensitivity analyses were undertaken using variations to key input parameters. RESULTS: Compared to ipilimumab, nivolumab therapy over 10 years would lead to an improvement in survival of 1.58 years and 1.30 QALYs per person, at a (discounted) net cost of AUD$77,119 per person. These equate to ICERs of AUD$48,851 per year of life saved and AUD$59,311 per QALY saved.  CONCLUSIONS: Compared with ipilimumab, nivolumab represents a cost-effective means of improving outcomes among Australian patients with AM.