The cure rate for childhood acute lymphoblastic leukemia (ALL) differs markedly between developed and developing countries. To assess the effect of a multidisciplinary team approach and protocol-based therapy on the event-free survival of children with ALL in an area with limited resources. DESIGN, POPULATION, AND SETTING: A retrospective cohort study at a pediatric hospital in the resource-poor city of Recife, Brazil. We reviewed medical records of the outcomes of 375 children with ALL diagnosed between 1980 and 2002. Eighty-three children were diagnosed in the early period (1980-1989), in the absence of a dedicated pediatric oncology unit, protocol-based therapy, specially trained nurses, 24-hour on-site physician coverage, and ready access to intensive care. Seventy-eight children were treated (all according to protocol) during the middle period (July 1994 to March 1997). During the recent period (April 1997 to December 2002), 214 children were treated with protocol in a dedicated pediatric oncology unit staffed 24 hours by pediatric oncologists and oncology nurses. Improvements were implemented gradually during the middle period and were completed during the recent period. Event-free survival was estimated by the Kaplan-Meier method. Events included death from toxicity, disease progression or relapse, and abandonment of treatment. The 5-year event-free survival improved steadily: 32% (95% CI, 21%-43%) in the early period, 47% (95% CI, 36%-58%) in the middle period, and 63% (95% CI, 55%-71%) in the recent period. The probability of cause-specific treatment failure in the early, middle, and late periods, respectively, within 1 year of diagnosis was 14% vs 3.8% vs 3.3% for relapse; 6.0% vs 12% vs 9.8% for death from infection; 2.4% vs 13% vs 4.2% for death from noninfectious toxicity; and 16% vs 1.3% vs 0.5% for abandonment of therapy. Treatment of childhood ALL in a dedicated pediatric oncology unit using a comprehensive multidisciplinary team approach, protocol-based therapy, and local support and funding is associated with improved outcomes in a resource-poor area.