The objective of the study was to evaluate the outcomes of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases using stereotactic radiosurgery (SRS) in the tyrosine kinase inhibitor (TKI) era. Sixty-one patients (226 metastases) were treated using Gamma-Knife and 63 patients (136 metas-tases) using linear accelerator. The association of SRS with TKI is highly efficient in brain metastases from RCC and, appears safe and avoids whole-brain radiotherapy. Background: The objective of the study was to evaluate the outcomes in terms of efficacy and safety of a large consecutive series of 362 patients with renal cell carcinoma (RCC) brain metastases treated using stereotactic radi-osurgery (SRS) in the tyrosine kinase inhibitor (TKI) era. Patients and Methods: From 2005 to 2015, 362 consecutive patients with brain metastases from RCC were treated using SRS in 1 fraction: 226 metastases (61 patients) using Gamma-Knife at a median of 18 Gy (50% isodose line); 136 metastases (63 patients) using linear accelerator at a median of 16 Gy (70% isodose line). The median patient age was 58 years. At the first SRS, 37 patients (31%) received a systemic treatment. Among systemic therapies, TKIs were the most common (65%). Results: The local control rates were 94% and 92% at 12 and 36 months, respectively. In multivariate analysis, a minimal dose >17 Gy and concomitant TKI treatment were associated with higher rates of local control. The overall survival rates at 12 and 36 months were 52% and 29%, respectively. In multivariate analysis, factors associated with poor survival included age !65 years, lower score index for SRS, concomitant lung metastases, time between RCC diagnosis and first systemic metastasis 4 months, occurrence during treatment with a systemic therapy, no history of neurosurgery, and persistence or occurrence of neurological symptoms at 3 months after SRS. Seventeen patients had Grade III/IV adverse effects of whom 3 patients presented a symptomatic radionecrosis. Conclusion: SRS is highly effective in patients with brain metastases from RCC. Its association with TKIs does not suggest higher risk of neurologic toxicity.