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Background and Purpose: As patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location., Materials and Methods: We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12-17 fractions HFRT at our institution between 2015-2022. Clinical scenarios included: unresectable, locoregional only disease (26 %); oligometastatic disease (<3 total sites, 17 %); oligoprogressive disease (<3 sites progressing, 17 %); and aggressive palliation (>5 known sites of disease or with at least 3 sites progressing, 40 %)., Results: Of the 53 HFRT targets, 91 % (n = 48) had radiographic evidence of response as defined by either stabilization (6 %, n = 3), decreased size (74 %, n = 39), or decreased FDG avidity (11 %, n = 6). Of the 43 symptomatic patients, 98 % (n = 42) had symptomatic improvement. One -year local control was 79 %, with 2-year progression-free and overall survival of 33 % and 39 % respectively. The most common acute toxicities were radiation dermatitis (16 %, n = 8) or a pain flare (14 %, n = 7). Late toxicities were uncommon and typically grade 1., Conclusion: HFRT provides favorable local control and symptomatic relief with limited toxicity in tumors not amenable to surgical resection or stereotactic ablative RT., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Amaria reported receiving research funding from Obsidain and OnKure pharma companies outside the scope of the submitted work. Dr. McQuade reported receiving consultation fees from Merck and honoraria from Bristol Myers Squibb and Roche outside the scope of the submitted work. Dr. Glitza reported receiving consultation fees from Biodexa, Everclear and Midatech in addition to speaker fees from Novartis andPfizer. She also reported receiving research support from BMS, MERCK and Pfizer. And she serves on the advisory board of BMS, Novartis, and Pfizer outside the scope of the submitted work. Dr. Diab reported receiving compensation from Memgan for advisory board membership outside the scope of the submitted work. Dr. Ross reported receiving research funding from AMGEN Pharma and travel expenses from Merck Pharma outside the scope of the submitted work. No other disclosures were reported., (© 2024 The Authors.)