OBJECTIVES: To review the efficacy and safety of sunitinib in comparison with other drugs for first-line treatment in metastatic renal cell carcinoma. METHODS: We performed a systematic review that evaluated sunitinib compared to bevacizumab plus interferon alfa, pazopanib, and sorafenib in patients with metastatic renal cell carcinoma without previous treatment.  The search was performed using Medline, EMBASE, Cochrane, LILACS, and DARE databases and was restricted to randomized clinical trials (RCT). The RTCs were selected and extracted, and risk of bias was assessed, using the Cochrane checklist by two researchers independently. Bayesian mixed treatment comparison (MTC) method was applied for the pairwise comparisons among treatments. The outcomes were: overall survival (OS), progression free survival (PFS), response rate and serious adverse events (SAE). RESULTS: We found 166 references, from which 5 RCTs met the inclusion criteria. The principal comparator in the studies was interferon alfa with the exception of one study (Motzer 2013) with a direct comparison between sunitinib and pazopanib. For PFS, sunitinib showed better results than bevacizumab plus interferon alfa (HR 0.79; 95% CrI 0.66-0.96), and sorafenib (HR 0.60; 95% CI 0.44-0.84); PFS in comparison to pazopanib was similar (HR 0.94; 95% CrI 0.81 – 1.10). Sunitinib was similar in terms of OS to bevacizumab plus interferon alfa (HR 0.93; 95% CrI 0.76 – 1.13), and pazopanib (HR 0.91; 95% CrI 0.78 – 1.06). In terms of proportions of SAE, sunitinib was safer than bevacizumab plus interferon alfa (OR 0.35; 95%CrI 0.12 – 0.97),  tends to be safer but without statistically significant difference than pazopanib (OR 0.76; 95% CrI 0.33-1.74), and similar  than sorafenib (OR 1.03; 95% CrI 0.25 -4.28). CONCLUSIONS: The MTC suggests that sunitinib as first line of treatment of metastatic renal cell carcinoma is a reliable option due to its efficacy and safety profile compared with other alternatives.