OBJECTIVES: Renal cell carcinoma (RCC) is the most common renal tumor and accounts for 2 to 3% of all adult malignancies. Up to 30% of patients with renal-cell carcinoma present with metastatic disease. The aim of the study was to assess the cost-effectiveness of first-line medications for patients with metastatic RCC from the payerʼs perspective. METHODS:  A Markov model was developed using 6-week cycles for evaluating the cost-effectiveness of four mRCC first-line therapies: Interferon-α (3 million units (MU)/day 3 times-per-week for first week; 6MU/day 3 times-per-week for second week, 9MU/day 3 times per-week third week onward), sunitinib (50mg/day 4 weeks ON + 2 weeks OFF), sorafenib (400mg/twice-a-day) and bevacizumab plus Interferon α (10mg/kg/bi-weekly + 9MU 3 times-per-week every 3 weeks). The model had a 10-year time horizon. The four model stages were: No progression, progression, best supportive care and death. Effectiveness data were obtained through a systematic review, resource utilization were collected from a Colombian Delphi Panel, and costs included were retrieved from Colombian tariff manual (SOAT).  Effectiveness was measured by progression-free life years (PFLY) and life-years gained (LYG). Costs and outcomes were discounted with a 3% annual rate. Univariate sensitivity analysis was developed.  RESULTS:  Sunitinib showed higher overall mean costs per patient (US$ 5,215.48) compared to interferon; while comparing against sorafenib and bevacizumab + interferon sunitinib costs per patient revealed to be lower in US$12,946.01 and US$ 102,780.16 respectively. Sunitinib had the higher effectiveness results: 1.35 PFLY, 2.9 LYG and 1.87 QALY. Incremental cost-effectiveness analysis shows sunitinib is cost-saving compared to sorafenib and to the combination of bevacizumab + interferon, and compared to monotherapy with interferon the incremental cost-effectiveness ratio (ICER) per LYG for sunitinib was US$12,099, per PFLY was US$8,381 and per QALY was US$14,901. CONCLUSIONS: This analysis indicates that sunitinib represents the most cost-effective option for first-line mRCC treatment in Colombia.