In acute myeloid leukemia (AML), leukemogenesis depends on cell-intrinsic genetic aberrations and, therefore, studies on AML require investigations in an in vivo setting as provided by patient-derived xenograft (PDX) models. Here we report that, next to leukemic cell characteristics, recipient sex strongly influences the outgrowth of AML cells in PDX models, with females being much better repopulated than males in primary as well as secondary transplantation assays. Testosterone may be the more important player since, strikingly, better engraftment was seen in castrated male recipients than in control ones, while ovariectomy did not significantly impair engraftment in females. Shorter time to engraftment and mouse survival were observed in cases with adverse molecular risk, and respectively with a high ratio of FLT3-ITD mutated AML cells. Furthermore, cases of adverse-risk AML showed higher percentages of phenotypic leukemic stem cells, suggesting impaired differentiation capacity in these AML subtypes. Overall, we achieved successful repopulation with 14/23 (61%) favorable-risk, 18/30 (60%) intermediate-risk and 4/8 (50%) adverse-risk AML cases in female recipient PDX models. Our data identify recipient sex as an important experimental confounder in leukemia PDX models, and the contribution of the sex hormones to leukemogenesis as an intriguing, underexplored area for research.