*Purpose: Previous studies of sex differences in heart transplant outcomes focused on interactions between donor and recipient sex, but did not consider the potentially modifying effect of recipient age. The relationship between recipient sex and kidney transplant outcomes is modified by both donor sex and recipient age. We hypothesized that young female heart transplant recipients have a higher risk of graft failure than young males, whereas at older ages the risk of graft failure does not differ by recipient sex.

*Methods: We conducted a retrospective cohort study of all first heart transplant recipients recorded in the SRTR (1988-2018). We used Cox models, stratified on donor sex, to evaluate the association between recipient sex and graft failure (defined as re-transplantation or death after graft failure). We included an interaction between recipient sex and recipient age, which was treated as a time-varying variable, and adjusted for potential confounders.

*Results: Among 47,865 male and 16,877 female heart transplant recipients, 5589 males and 2509 females experienced graft failure. When the donor was female, no significant differences were observed in the risk of graft failure between female and male recipients of any age, although among recipients < 30y females had a higher risk than males. When the donor was male, female recipients of all ages had higher risks of graft failure than males, with statistically significant differences in the 13-29 y, and ≥45 y intervals.

*Conclusions: Reaction of females against the HY antigen may contribute to higher graft failure risks among female recipients of a male donor. More work is needed to identify other factors contributing to the observed differences.

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