Background: Heart transplantation is limited by the supply of donor organs. Previous studies have associated female donor to male recipient with decreased posttransplant survival. We wanted to evaluate whether this risk can be mitigated using higher donor than recipient body mass index (BMI). Methods: We performed a retrospective analysis of the Organ Procurement and Transplantation Network/United Network of Organ Sharing registry encompassing years 2005 to 2018 for all male adult recipients (>18 years of age) who underwent isolated heart transplantation with grafts from female donors. The association between donor and recipient BMI difference and recipient survival was evaluated using adjusted Cox proportional hazards modeling. Results: A total of 3788 male recipients who received female donor hearts met inclusion criteria for analysis. Maximally selected rank statistics identified donor minus recipient BMI of 1.5 kg/m2 as a meaningful cutoff point in the analysis of recipient survival. Multivariable Cox proportional hazards analysis demonstrated that increasing donor BMI relative to recipient BMI up to this cutoff point was associated with improved survival (hazard ratio per 5-unit difference, 0.87; 95% confidence interval, 0.77-0.99). Above this cutoff point, increasing donor BMI relative to the recipient did not improve survival more than what was achieved by adding 1.5 of BMI difference (hazard ratio per 5-unit difference, 0.97; 95% confidence interval, 0.90-1.04). Conclusions: Increasing donor BMI relative to recipient BMI up to 1.5 kg/m2 greater than recipient BMI was associated with improved survival. BMI difference may be useful as a simple surrogate for predicted heart mass difference to help mitigate the impact of sex mismatch in heart transplantation.