OBJECTIVES This study estimated the cost-utility of axitinib after sunitinib failure in adult patients with renal cell carcinoma. Total costs and quality adjusted life years accrued with axitinib was compared to everolimus, the only drug for second line treatment financed by the Portuguese National Health Service.  METHODS A 4-week cycle Markov model with three health states (progression free, post progression, and death) was adapted to the Portuguese setting. In the absence of head-to-head clinical trials and the unfeasibility of a standard indirect comparison, relative efficacy was based on a previous simulated treatment comparison. Axitinib trial data on quality of life (utility) was used for the progression free stage and assumed equal for everolimus, while utilities for the post progression stages were obtained from the literature. Resource use was determined by a panel of five experienced experts to reflect Portuguese clinical practice. Official unit costs were used, following the Portuguese National Health Service perspective. The model adopted a lifetime frame (15 years) with a 5%discount rate.  RESULTS Axitinib allowed an increment of 0.20 years of progression free survival, 0.53 years of overall survival, and 0.32 quality adjusted life years compared to everolimus. Despite having a similar daily cost, the use of axitinib implied an incremental cost of 9,100€, mainly due to the increase in progression free survival, that matches second line treatment duration. Consequently the cost per quality adjusted life year was 28,598€. Sensitivity analyses showed that results were robust to model parameters specification, with the main uncertainty source being clinical efficacy.  CONCLUSIONS Axitinib increased progression free and overall survival, which allowed patients to benefit from more quality adjusted life years at a cost increase. Overall, it was possible to advocate that axitinib is cost-effective, as the cost per QALY is below commonly accepted thresholds.