OBJECTIVES: The objective of this study was to conduct a cost-effectiveness analysis of everolimus versus axitinib for the treatment of metastatic RCC (mRCC) in Greece. Everolimus and axitinib were the only approved therapies with category 1 recommendation for second-line treatment of metastatic renal cell carcinoma (RCC) following TKI therapy, according to NCCN guidelines, by the time this analysis was conducted (Dec. 2015). METHODS: A Markov model was used to evaluate the cost-effectiveness of everolimus versus axitinib from a third-party payer perspective over a 10-year time horizon. Efficacy and safety inputs were based on a weight-adjusted indirect comparison of the therapies using the respective phase 3 trial data, RECORD1 and AXIS (Motzer et al., 2010; Rini et al., 2013). Utility values were calculated based on a time trade-off (TTO) study and adverse events rates from RECORD-1 and AXIS trials (Swinburn et al., 2010). Resource use and adverse events management data were collected by DELPHI method from an expert panel of clinicians from private and public hospitals in Greece. Direct medical costs were included (i.e. pharmaceutical, physician visits, lab and imaging tests and management of AEs). An annual discount rate of 3.5% was applied to the health state costs and efficacy values. The incremental cost-effectiveness ratio (ICER) was calculated. A threshold of €35,000 per QALY gained was used, per WHO Guidelines. Probabilistic sensitivity analysis (PSA) was conducted. RESULTS: Everolimus was less costly and more effective (“dominant”) compared with axitinib, with €5,495 lower lifetime costs per patient and 0.017 greater discounted QALYs (€10,175 vs €15,671 and 0.617 vs 0.599). PSA suggests these results are robust; the probability that everolimus is cost-effective vs axitinib was estimated to be 72.5% given the ICER threshold. CONCLUSIONS: Everolimus is likely to be dominant compared with axitinib as second-line treatment of mRCC in the Greek healthcare setting.