Although keloids have been empirically treated using steroids and radiation, evidence-based radiation parameters for keloid therapy are lacking.To determine evidence-based radiation parameters for blocking keloid fibroblast proliferation in vitro and apply them to patients.The effects of various radiation parameters and steroids on cell proliferation, cell death and collagen production in keloid explants and fibroblasts were evaluated using standard assays. Effective radiation parameters were then tested on patients.No differences were observed between the effects of 50kV and 320kV X-rays or between single and fractionated radiation doses on keloid fibroblasts. A 3Gy, 50kV dose inhibited keloid fibroblast proliferation in culture, while 9Gy completely blocked their outgrowth from explants by inducing multiple cell death pathways and reducing collagen levels. Thirteen of fourteen keloids treated with a single 8Gy, 50kV dose of radiation did not recur, though 4 patients with 6 keloids were lost to follow up.75% of patients received steroids for pruritus, while ∼25% of patients were lost to follow up.A single 8Gy dose of superficial 50kV radiation delivered an average of 34 days following keloid excision maybe sufficient to minimize recurrence, including those resistant to steroids. Higher radiation energies, doses or fractions maybe unnecessary for keloid therapy.