Background: A significant number of patients who receive palliative irradiation for painful bone metastases experience pain flare, defined as a distressing transient increase in pain not immediately controlled by additional analgesics. This pain is postulated to be due to edema at the onset of radiotherapy. This study aims to compare the incidence of bone pain flare among patients who receive steroid prophylaxis to those with no prophylaxis treatment.Methods: From June 2011 to June 2013, 147 eligible patients with painful bone metastases entered into this phase 3 prospective study. We divided patients into two groups. Group A received 8 mg dexamethasone one hour prior to irradiation during the treatment time and for three days afterwards. Group B received no prophylaxis treatment. All patients received radiotherapy at a dose of 2000 Gy/5 fractions. The development of flare was recorded in each group and several factors were examined to determine the presence of an influence on this incidence.Results: Group A included 68 patients, 11 (16.2%) of whom developed bone pain flare while group B comprised 79 patients, 30 (38%) with bone pain flare. These results indicated that steroid prophylaxis made a statistically significant difference in decreasing pain flare incidence (P=0.0033). No steroid related complications were reported by any of the patients. None of the factors assessed showed a statistically significant effect on flare development (P>0.05).Conclusion: Administration of 8 mg of dexamethasone an hour prior to irradiation for the treatment period and three days afterwards is effective in significantly decreasing the incidence of pain flare. Dexamethasone is well tolerated and may be recommended for all adult patients who undergo palliative bone irradiation who have no contraindi- cation to this treatment. Larger phase 3 randomized trials are needed to confirm these findings.