Allogeneic hematopoietic stem cell transplantation (HSCT) has not been widely used in patients with acute myeloid leukemia (AML) and Down syndrome (DS) due to fear of transplantation-related toxicity. A retrospective analysis of the outcome of allogeneic HSCT was conducted in 15 patients with AML and DS. The five patients transplanted with the reduced intensity conditioning (4 in complete remission (CR) and 1 in non-CR) had a significantly better survival rate than 10 patients transplanted with a conventional conditioning (4 in CR and 6 in non-CR) (3-year EFS (95% confidence interval): 80.0% (20.4–96.9%) vs. 10.0% (0.6%–35.8%), P = 0.039). Pediatr Blood Cancer 2014;61:925–927. © 2013 Wiley Periodicals, Inc.