Background: The management of melanoma with multiple brain metastases (MBM) is complex given improvements in targeted agents, immunotherapy, and radiotherapy. Whole brain radiation therapy (WBRT) is a radiotherapy technique with limited outcomes data. We report our institutional outcomes for MBM patients receiving WBRT and assess whether certain clinical factors impact prognosis. Methods: A retrospective review of a single institution database was performed. Patients diagnosed with MBM from 2000-2018 treated with WBRT, with or without systemic treatments, were included. Post-WBRT brain MRI scans were assessed at timed intervals for radiographic response. Clinical and treatment variables associated with overall survival (OS), progression free survival (PFS), intracranial failure-free survival (IFFS), and local failure-free survival (LFFS) were assessed. Data was collected on radiation-induced side effects, including radionecrosis, hemorrhage, and memory deficits. Results: Of 1347 patients treated with WBRT from 2000-2018, 63 patients had melanoma. 69% of patients had ≥5 brain metastases at the time of WBRT, 68% had extracranial disease, and 71% received steroids during their overall treatment course. Most had received previous therapies and had WBRT as a last resort. Median WBRT dose was 30 Gray over 10 fractions. Median follow-up was 4.0 months. Six-month OS, PFS, IFFS, and LFFS were 52.7%, 20.4%, 52.3%, and 43%. Median OS, PFS, IFFS, and LFFS were 7.0 months, 2.2 months, 6.1 months, and 4.9 months. Performance status correlated with OS on univariate and multivariate analysis. BRAFi was the only systemic therapy to significantly impact OS on univariate analysis (HR 0.24, 95% CI 0.07-0.79, p = 0.019), although this was not seen on multivariate analysis. There was a 19% rate of memory deficits. Among the 46 patients with post-WBRT brain scans, 17% had radionecrosis and 28% had intralesional hemorrhage. Not all radiographically noted radiotoxicities were clinically significant, although hemorrhage decreased IFFS on both univariate and multivariate analysis. Conclusions: Outcomes for MBM patients receiving WBRT indicate that WBRT remains a worthy option to control intracranial disease. Treatment-related effects such as hemorrhage, necrosis, or cognitive changes are considerations. Median PFS and IFFS suggest that systemic disease control continues to be the greater issue. The role of WBRT should be re-evaluated in the modern era, which features advanced imaging detection ability, newer systemic agents, and improved steroid avoidance strategies.