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Aims: This study aimed to evaluate the symptomatic efficacy and tolerability of three different radiotherapy (RT) regimens for patients with vertebral metastases in a low-middle-income country setting, focusing specifically on the effectiveness of single-fraction radiotherapy., Methods: Conducted at the National Institute of Cancer Research and Hospital, Bangladesh, from July 1, 2020, to June 30, 2021, this prospective, non-randomized study enrolled 90 patients aged 18 to 75 years with histologically confirmed primary malignancies and vertebral metastases. Patients were allocated to one of three treatment arms: 8 Gy in a single fraction (Arm A), 20 Gy in 5 fractions (Arm B), or 30 Gy in 10 fractions (Arm C). The primary endpoint was pain response at 12 weeks, assessed by the Visual Analogue Scale and International Bone Metastases Consensus. Secondary endpoints included toxicity, measured by the Common Terminology Criteria for Adverse Events, and overall survival., Results: Pain control at 12 weeks showed no significant differences among the treatment groups, with 70% of patients in Arm A, 67% in Arm B, and 70% in Arm C experiencing either partial or complete pain relief (p = 0.95). The overall survival rates were comparable across the groups (median survival, 7 months for arms A and C, 6 months for Arm B). Skin toxicity was significantly lower in Arm A (10% incidence) compared to arms B (30%) and C (47%) (p = 0.017). There were no reports of Grade 3 or higher toxicities., Conclusion: The study confirms the efficacy and safety of single-fraction RT for spinal bone metastases, providing significant pain relief and lower skin toxicity relative to multiple fraction regimens. These results confirm the efficacy of single-fraction RT in the treatment of vertebral metastases also in resource-limited settings, suggesting its broader adoption to reduce toxicity and treatment burdens in low-middle-income countries., Competing Interests: Declarations. Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the National Institute of Cancer Research and Hospital, Dhaka, Bangladesh. Informed consent statement: Informed consent was obtained from all subjects involved in the study. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)