OBJECTIVES: To evaluate the cost-effectiveness of sorafenib plus best supportive care (BSC) versus BSC alone in advanced renal cell carcinoma (RCC) from the perspective of the Spanish National Health Service. METHODS: A Markov model was developed to project the lifetime survival and costs associated with sorafenib plus BSC and BSC alone. The model tracked patients with advanced RCC through three disease states – progression free survival (PFS), progression, and death. Transition probabilities between disease states varied for each 3-month period and were obtained from a clinical trial. Quality-Adjusted-Life-Years (QALY) gained were used as a measure of treatment effectiveness. Resource utilization included drug, administration, physician visits, monitoring, and adverse events. Costs and survival benefits were discounted annually at 3%. All costs were adjusted to 2005 Euros. Scenario sensitivity analyses were conducted. RESULTS: The lifetime per patient costs were €44,904 and €10,502 for sorafenib plus BSC and BSC alone, respectively. The incremental cost-effectiveness ratio (ICER) of sorafenib plus BSC versus BSC alone was €37,667 per QALY gained. The key drivers of the model results were survival after progression and PFS probabilities for both treatment groups. Sensitivity analyses showed that the model results were robust to variance in sorafenib and BSC treatment costs. CONCLUSION: Sorafenib is a cost effective therapy in the management of advanced RCC. Sorafenib offers a unique opportunity to prolong PFS and overall survival in those patients, and has the potential of offer considerable value to patients with minimal budget impact to the NHS in Spain.