Children with acute leukemia may experience high treatment-related mortality, which often occurs early in the induction phase. The aim of the study was to assess the incidence and risk factors related to increased mortality during induction therapy of pediatric patients with acute leukemia. This is a retrospective study that included pediatric acute leukemia patients who presented to the National Cancer Institute, Cairo University, between January 2011 and December 2013. The study included 370 patients, 253 with acute lymphoblastic leukemia, 100 with acute myeloid leukemia, and 17 with mixed phenotype acute leukemia. The total and induction death rates were 40.5% and 19.2%, respectively. Most of the early deaths were attributed to infections (64.7%) and cerebrovascular accidents (18.3%). Using enhanced supportive care measures during 2013 had significantly reduced the overall and induction mortality rates (29% and 13.6%, respectively, in 2013 vs. 46% and 20.3% in 2011). Induction deaths in pediatric acute leukemia remain a major challenge in developing countries, and using enhanced supportive care measures is effective to improve the survival outcome in this group of patients.