OBJECTIVES: To evaluate the cost-effectiveness of Everolimus as second-line of treatment compared with sorafenib in adult patients with metastatic renal cell carcinoma, from the perspective of the Mexican Public Health Institution METHODS: We compare the results obtained in treating renal cancer patients with either sorafenib or everolimus, previously treated with sunitinib in Mexico. We developed a markov model in a two-year period among three possible health states (stable, progression and death). Overall survival and progression-free survival were used as effectiveness measures and the sources of this information were published articles. We considered the costs of drugs, best-supportive care and follow-up (stable disease and progression); drug costs of everolimus and sorafenib only apply to stable patients. The costs of medical resources correspond to the costs of medical care in tertiary care systems. All costs were calculated in 2010 Mexican pesos. An incremental analysis of cost and results in health was realized, to compare everolimus and sorafenib. A sensitivity analysis was also accomplished (deterministic and probabilistic). The discount rate applied to costs and effectiveness was 5%. RESULTS: Patients with everolimus obtained more overall survival (14.37 vs. 7.73 months) and progression-free survival (4.83 vs. 3.88 months) than those that used sorafenib.  Everolimus resulted as the alternative with less average total cost than sorafenib: $391,765.00 and $454,802.00 respectively. Everolimus is a dominant option compared with sorafenib. Sensitivity analysis showed robustness in the results CONCLUSIONS: Everolimus is the cheapest treatment option and saving of resources, which significantly increases the survival of patients and provides longer progression-free and more overall survival versus sorafenib.