Background: Bone is the most common site for metastases in cancer and may complicate a wide range of malignancies. Radiotherapy is a successful and efficient method for pain palliation and it can prevent the morbidity of bone metastases. Pain flare is a common event, occurring in almost 40% of the patients that receive palliative radiotherapy. Dexamethasone has shown possibility for prevention of such flare. Objective: This study aimed to investigate the efficacy of dexamethasone as prophylaxis for radiotherapy-induced pain flare in cases of painful bone metastases. Patients and Methods: Prospective randomized control trial was conducted at the Oncology and Nuclear Therapy Unit, Suez Canal University Hospital. The study involved 129 patients. Patients with painful bone metastases were divided into two groups, Study group received 8 mg dexamethasone first day of radiotherapy then for three days after finishing treatment, while control group received radiotherapy only. Results: The mean age in study group was 60.59 ± 7.64 years in comparison to 59.85 ± 7.02 years in control group. The most common primary sites were breast and prostate cancer. Incidence of pain flare was 8.8% of patients among study group while 19.7% of patients among control group. The difference between both groups was statistically non-significant. Conclusion: Dexamethasone does not play a significant role in reducing pain flare after palliative radiotherapy on painful bone metastases.