The outcome of acute lymphoblastic leukemia (ALL) in developing countries is inferior compared with the resource-rich nations. This descriptive study was designed to determine the pattern of deaths in children with ALL treated at a single center and identify the problem areas in management. Case records of 532 patients with ALL were analyzed. Information regarding the clinical-demographic profile, therapy, and course of illness were recorded. One hundred twenty-eight (24.0%) deaths were recorded. Sepsis (53.3%) and bleeding (15.7%) were the most common causes of mortality. The mortality rate fell significantly during the induction and remission phases of the therapy in 2 consecutive time periods between 1990 to 1997 and 1998 to 2006. The factors associated with an increased risk of death were longer symptom diagnosis interval (P=0.049), bulk disease (P=0.008), mediastinal adenopathy (P=0.001), higher total leukocyte count (P=0.001), and lower platelet count (P=0.007) at presentation as compared with the survivors. Multivariate analysis showed that longer symptom diagnosis interval (P=0.001), mediastinal adenopathy (P=0.006), lower platelet count (P=0.001), and higher total leukocyte count significantly influenced death. The estimated median time to death for the induction and remission deaths were 0.5 and 17 months, respectively. A high mortality rate necessitates the reappraisal of our treatment protocols. Many deaths should be avoidable by the provision of adequate supportive care, close supervision during and after chemotherapy, and appropriate antibiotic and antifungal therapy.