Purpose To assess the efficacy and toxicity of hypofractionated radiotherapy (RT) alone in treatment-resistant symptomatic keloids. Methods Six patients with a total of 13 inoperable large keloid lesions and no response to previous treatments were admitted to our department between 2017 and 2019. All patients were examined for detailed wound localization, size, contour, and color assessment, and for objective and subjective symptoms. Response to treatment was graded as "complete remission" in case of full symptomatic relief and >75% decrease in lesion size, as "partial remission" in case of partial symptomatic relief and 25-75% decrease in lesion size, and as "stable disease" in case of no symptomatic relief or Results A total dose of 37.5 Gy external RT in five fractions was prescribed by 6-MeV electrons in 4 patients and 6-MV photons in 2 patients. Complete response was obtained in all patients at the 6-month control. All patients were satisfied with cosmetic results at their last control. Grade 2 dermatitis developed in all patients during the second week of RT but resolved completely in all after 6 months following the end of RT. Conclusion In keloids that are unresponsive to standard treatment, hypofractionated RT using a total dose of 37.5 Gy in five fractions is feasible.