Survival of adults with acute lymphoblastic leukemia (ALL) is inferior to that of pediatric patients. Strategies to improve the outcome of adult population are warranted. This study aims to evaluate the efficacy and safety of pediatric-inspired regimens given to adolescents and young adults (AYA), usually defined as 16–39 years, with ALL. Systematic review and meta-analysis of comparative trials of AYA patients with ALL given induction chemotherapy with either pediatric-inspired regimens or conventional-adult chemotherapy was conducted. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Our search yielded 11 trials, including 2,489 patients. AYA patients given pediatric-inspired regimens had a statistically significant lower all cause mortality rate at 3 years (RR 0.58; 95% CI 0.51–0.67). Complete remission rate after induction chemotherapy and event free survival were superior in the pediatric-inspired regimens arm (RR 1.05; 95% CI 1.01–1.10 and RR 1.66; 95% CI 1.39–1.99, respectively). Relapse rate was also lower in patients given pediatric-inspired regimens (RR 0.51; 95% CI 0.39–0.66) with comparable nonrelapse mortality between the two groups (RR 0.53, 95% CI 0.19–1.48). Pediatric-inspired regimens are superior to conventional-adult chemotherapy in AYA ALL patients. Further randomized controlled studies to investigate this approach in adult ALL patients are warranted. Am. J. Hematol. 87:472–478, 2012. © 2012 Wiley Periodicals, Inc.