OBJECTIVES Metastatic Renal cell carcinoma (mRCC), the most prevalent kidney cancer, is a rare malignancy with a poor prognosis; fewer than 10% of patients with metastatic disease survive beyond 5 years. The purpose of the study was to model the economic and health consequences of first-line treatments in adult patients with mRCC in stages III and IV from an institutional perspective. METHODS A cost-effectiveness analysis was developed using a stochastic Markov modeling approach. The model simulates treatment costs, progression free-months (PFM) and overall survival (OS) in a three-year period among four possible health states (no new progression, death due to mRCC, history of new progression and death due to other causes). The model compared in a six-week cycles: sunitinib 50mg/day vs. sorafenib, bevacizumab+IFN-alpha and IFN-alpha alone (baseline). Transition probabilities were obtained from previously published trials. Resource use and costs data were obtained from randomized hospital records at Hospital de Oncologia CMN "Siglo XXI" in Mexico City (n=35). Both costs and effectiveness were discounted using a 3% annual rate. One-way and probabilistic sensitivity analyses were performed and acceptability curves were constructed. RESULTS First-line treatment with sunitinib showed the highest PFM and OS (10.1 and 19.9 months) followed by bevacizumab+IFN-alpha (9.4 and 19.1 months); sorafenib(5.1 and 17.3 months) and IFN-alpha alone(4.72 and 16.35 months). Expected health care costs for sunitinib in the three-year follow-up period resulted in US$49,181; bevacizumab+IFN-alpha (US$95,363); sorafenib (US$50,265) and IFN-alpha alone (US$29,000). The ICER's per PFM and OS resulted in US$3767.0 and US$5668.8 (sunitinib vs. IFN-alpha alone). Results were robust to second-order Monte Carlo sensitivity analysis (10,000 iterations). Acceptability curves showed that sunitinib would be a cost-saving strategy against sorafenib and bevacizumab+IFN-alpha with a probability over 70%(p<0.05). CONCLUSIONS Results show that sunitinib as first-line treatment is a cost-effective alternative among the new agents for patients with mRCC.