Purpose: To find the fastest and most effective/efficient method to economically deliver fractionated half-body irradiation (HBI) for widespread (WS), symptomatic, metastatic bone cancer. Methods and Materials: A Phase III trial with 3 HBI arms: (Arm A) Control (15 Gy/5 fractions/5 days); (Arm B) Hyperfractionation (HF) (8 Gy/2 fractions/1 day); (Arm C) Accelerated HF (12 Gy/4 fractions/2 days). Six countries randomized 156 patients (all with WS bone metastases): 51, 56, and 49 patients to Arms A, B, and C, respectively. There were 72 (46%) breast, 50 (32%) prostate, 9 (6%) lung, and 25 (16%) miscellaneous primary tumors. Initial performance status (PS) was 1–2 in 101 (65%) and PS 3–4 in 55 (35%). The lower, upper, and middle halves of the body were treated 79, 68, and 9 times. Results: Pain relief was seen in 91% of patients (45% complete [CR] and 46% partial [PR]) within 3–8 days. Overall (OS), median (MST), and pain-free (PFS) survival was 174, 150, and 122 days. Breast tumors had a higher OS (279 days) than that of other primary tumors, but when analyzed by treatment, was not significantly different than prostate tumors in Arm A. No survival differences were found in patients with PS 1–2 vs. 3–4, CR vs. PR, bone with/without visceral metastases, or by the number of metastases ( 15 bone lesions). Quality of life (QOL) assessed by the percent of the remaining life free of pain was 71%; furthermore significant improvements in PS, pain, and narcotic scores were seen after HBI. Toxicity was very acceptable (41% none, 50% mild/moderate, 12% severe but transitory); more was seen with upper HBI. Conclusion: In terms of response, time to response, OS, MST, PFS, QOL, and toxicity, schedules for Arms A and C were similar for all but prostate primaries. Schedule for Arm B, which delivered the lowest biologic dose in the shortest time, had significantly worse results in pain relief, OS, MST, PFS, and QOL. Results indicate that, for most primary tumor types (except prostate), delivering two HBI daily doses of 3 Gy in 2 consecutive days is as effective as delivering a daily dose of 3 Gy for 5 consecutive days. Thus, this is a faster and much more convenient HBI schedule for the palliation of pain in widespread cancer.