Menachem Bitan, Wensheng He, Mei–Jie Zhang, Hisham Abdel–Azim, Mouhab Fakhreddine Ayas, Bella Bielorai, Paul A. Carpenter, Mitchell S. Cairo, Miguel Angel Diaz, John T. Horan, Sonata Jodele, Carrie L. Kitko, Kirk R. Schultz, Morris Kletzel, Kimberly A. Kasow, Leslie E. Lehmann, Parinda A. Mehta, Nirali Shah, Michael A. Pulsipher, Tim Prestidge, Adriana Seber, Shalini Shenoy, Ann E. Woolfrey, Lolie C. Yu, and Stella M. Davies Abstract The safety and efficacy of reduced–intensity conditioning (RIC) regimens for the treatment of pediatric acute myeloid leukemia is unknown. We compared the outcome of allogeneic hematopoietic cell transplantation in children with acute myeloid leukemia using RIC regimens with those receiving myeloablative–conditioning (MAC) regimens. A total of 180 patients were evaluated (39 with RIC and 141 with MAC regimens). Results of univariate and multivariate analysis showed no significant differences in the rates of acute and chronic graft–versus–host disease, leukemia–free, and overall survival between treatment groups. The 5–year probabilities of overall survival with RIC and MAC regimens were 45% and 48%, respectively (P =.99). Moreover, relapse rates were not higher with RIC compared with MAC regimens (39% vs 39%; P =.95), and recipients of MAC regimens were not at higher risk for transplant–related mortality compared with recipients of RIC regimens (16% vs 16%; P =.73). After carefully controlled analyses, we found that in this relatively modest study population, the data supported a role for RIC regimens for acute myeloid leukemia in children undergoing allogeneic hematopoietic cell transplantation. The data also provided justification for designing a carefully controlled randomized clinical trial that examines the efficacy of regimen intensity in this population.