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Patients with brainstem metastases (BSMs) have minimal surgical options due to high-risk anatomy. To review our efficacy treating BSM using Gamma Knife stereotactic radiosurgery (SRS), we compared results on the basis of the utilization of mask-fixation (MF) or frame-fixation (FF). Data were retrospectively collected for 32 patients. Follow-up data for 49 lesions were analyzed for local control rate (LCR) and objective response rate (ORR). Primary cancers included lung, breast, and melanoma; most lesions were pontine. MF was used in 18 patients. Average tumor volume was 0.99 cm3 (0.005–13.3 cm3). Thirty-nine lesions were treated with single-fraction 16 Gy. Ten lesions were treated in 3–5 fractions with mean dose of 22.5 Gy. Mean follow-up was 14.2 months (1.2–48.2 months). One-year LCR was 94.7%. ORR at last follow-up did not differ between MF and FF (P = 0.81). Average reduction of lesion volume at 6 and 12 months did not differ between MF and FF (64% vs. 45%, P = 0.77; 70% vs. 77%, P = 0.78). Failure occurred in a pontine colorectal cancer metastasis mask-immobilized for treatment with 14 Gy. SRS for BSM achieved high LCR despite variability in tumor size and histology with no significant difference between MF and FF. Although trials have historically excluded patients with BSM, our data support SRS as a safe and efficacious treatment. This is the first study showing that MF provides equivalent, successful outcomes when compared with FF for patients with BSM. [ABSTRACT FROM AUTHOR]