BACKGROUND: Pediatric Diffuse intrinsic pediatric glioma (DIPG) remained dismal regardless of the new therapeutic and technical attempts. PURPOSE: To investigate the efficacy and toxicity of hypofractionated radiotherapy in pediatric DIPG compared to conventional radiotherapy and to determine the prognostic factors for its overall (OS) and progressionfree survival (PFS). PATIENTS AND METHODS: Sixty four children, below the age of 18 years, who presented to Children's Cancer Hospital, Egypt (CCHE) during the period July 2007 and July 2011 were randomized into 2 groups. The hypofractionated group received 39 Gy in 13 fractions in 21/2 weeks and the conventional arm receiving 55.8 Gy in 31 fractions in 6 weeks using conformal radiotherapy technique. The two arms were not different in age, gender, performance status and tumor volume. RESULTS: Thirty two children were randomized in each arm. The median OS for the whole group was 9.5 + 1.0 months: 7.4 + 1.0 months for the hypofractionated arm and 9.9 + 1.0 months for the conventional arm. The whole group has median PFS of 7.3 + 0.8 months; 7.0 + 1.4 months for the hypofractionated and 7.7 + 1.1 for the conventional arm. On the other hand, the 1-year and 2-year OS were 41.4 + 9.2% and 28.4 + 8,8% in the hypofractionated arm and 36.2 + 8.7% and 32.3 + 7.8% in the conventional arm. None of these differences was statistically significant. Furthermore, none of the tested factors (age, gender, performance status, tumor volume, radiation volume or tumor extension) proved to have statistically significant influence on OS or PFS. All patients showed marked degree of improvement in symptoms and signs with earlier response in the hypofractionated arm. The immediate and delayed side effects were not different between the 2 arms. CONCLUSIONS: Hypofractionated radiotherapy had similar overall, progression-free survival and delayed effect (in the long survivors) to conventional fractionation. It offers less burden on the patients, their families and the treating machines and departments.