OBJECTIVES: To model the cost-effectiveness of sunitinib versus sorafenib, temsirolimus and bevacizumab + interferon (IFN) as first-line therapy for mRCC in the Swedish health service setting. METHODS: An adapted Markov model was created using data collected from clinical trials. Patient-level data and parametric survival curves obtained from a comparative trial of sunitinib versus IFN were extrapolated to 10 years. Indirect comparison of the efficacy of sorafenib, temsirolimus and bevacizumab + IFN versus the IFN arm of clinical trials generated progression-free survival (PFS) and overall survival (OS) data. First-line therapy determined the choice of second-line therapy and the proportion of patients receiving best supportive care after progression. Resources specific to Sweden included drugs, tests, scans, monitoring, physician visits, hospitalisations and AE management. Outcome measures included life-years (LY), progression-free LY (PFLY), and quality-adjusted LY (QALY) gained. RESULTS: Sunitinib had the greatest projected PFS and OS. Incremental 10-year cost-effectiveness ratios for sunitinib versus sorafenib were Swedish krona (SEK) 120,300/PFLY, SEK177,900/LY and SEK210,200/QALY gained. Sunitinib dominated temsirolimus and bevacizumab + IFN, since both were more costly and less effective. At a threshold for societal willingness to pay of SEK500,000/QALY gained, sunitinib has the highest probability of being the most cost-effective therapy. In this model, key drivers were hazard ratios for PFS and OS, drug costs and the percentage of patients with second-line therapy. The update on PFS and OS for sunitinib and IFN presented at the ASCO 2008 meeting is in line with predicted values in the model and hence confirms the robustness of the results. CONCLUSIONS: In the Swedish health service setting, sunitinib is a cost-effective option for first-line mRCC therapy compared with sorafenib, temsirolimus and bevacizumab + IFN. Sunitinib had the highest probability of being the most cost-effective treatment at a SEK500,000/QALY threshold for societal willingness to pay for clinical benefit.