The toxicities associated with stereotactic radiosurgery (SRS) are an important factor when considering treatment options and supportive management for patients with brain metastases. We herein assessed the association between brain metastasis location and rates of toxicityafter SRS. We conducted a retrospective review of 170 patients treated with at least one course of SRS for brain metastases between 2008 and 2016 at our institution, and with subsequent follow up information. Typical SRS doses were 18-20 Gy in 1 fraction for lesions <2 cm, 18-21 Gy in 3 fractions for lesions 2-3 cm, and 25-30 Gy in 5 fractions for lesions >3 cm. Toxicity measures evaluated included radiation necrosis, seizure, and dexamethasone requirement, and comparisons between groups were analyzed by Fisher’s exact test and multinomial logistic regression. In the 170 patients, the median age at the time of the first SRS course was 61 years (range, 30-88 years). Histology included non-small cell lung cancer (35%), breast cancer (27%), melanoma (21%), renal cell cancer (5%), and other (12%). A total of 221 lesions treated during the initial SRS course were distributed among the frontal (29%), cerebellar (23%), parietal (16%), temporal (15%), occipital (14%), and other (including brainstem, thalamus, basal ganglia) (4%) regions. Median follow up duration was 8.6 months. SRS-related radionecrosis was noted in 4% of patients and seizure in 9%. Dexamethasone was used >3 months post-SRS in 23% of patients. Rates of radionecrosis significantly correlated with metastasis volume and prior whole brain radiotherapy (WBRT) but did not correlate with metastasis location or prior resection on multi-variable analysis (p<0.05). The radionecrosis rate was 1.1%, 5.7%, and 7.1% for lesions ≤1 cm3, 1-3 cm3, and >3 cm3, respectively, and 8.5% versus 2.5% for patients with and without prior WBRT. Risk of seizure was significantly higher in patients with primary motor or sensory cortex lesions compared to other locations, with 58% of seizures associated with motor cortex lesions and 16% associated with sensory cortex lesions (p<0.05). Of patients who initially presented with seizure and were on anti-epileptic medication at the time of SRS, 62% had no further seizures after SRS, while 38% did have post-SRS seizures, nearly all of whom had lesions in the motor strip. Only 5% of patients had new-onset seizure after SRS, and these were either related to lesion hemorrhage or location in the motor strip. In our series, brain metastasis location in the primary motor cortex was associated with higher rates of post-SRS seizure, including new seizures after SRS and breakthrough seizures while on anti-epileptic medication during SRS. Rates of radionecrosis were not associated with metastasis location but were associated with lesion volume and prior WBRT.