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We compared the safety and efficacy of ipilimumab and stereotactic radiosurgery (SRS) to SRS alone for newly diagnosed melanoma brain metastases (MBM).We reviewed records of newly diagnosed MBM patients treated with SRS from 2009 to 2013. The primary endpoint of overall survival (OS), and secondary endpoints of local control, distant intracranial failure, and radiation necrosis were compared using Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazards method.Fifty-four consecutive MBM patients were identified, with 20 (37.0%) receiving ipilimumab within 4 months of SRS. Ipilimumab-treated and non-ipilimumab–treated patients had similar baseline characteristics. No difference in symptomatic radiation necrosis or hemorrhage was identified between cohorts. Compared with patients in the nonipilimumab group, 1 year local control (71.4% vs. 92.3%, P=0.40) and intracranial control (12.7% vs. 29.1%, P=0.59) were also statistically similar. The ipilimumab cohort also had no difference in 1-year OS (37.1% vs. 38.5%, P=0.84). Patients administered ipilimumab within 14 days of SRS had higher 1-year (42.9%) and 2-year OS (42.9%) relative to ipilimumab delivered >14 days (33.8%, 16.9%) and SRS alone (38.5%, 25.7%) but these difference were not statistically significant. Univariate analysis and multivariate analysis both confirmed single brain metastasis, controlled primary, and active systemic disease as predictors for OS.Use of ipilimumab within 4 months of SRS seems to be safe, with no increase in radiation necrosis or hemorrhage; however, our retrospective institutional experience with this treatment regimen was not associated with improved outcomes.