Background: Sex-associated differences in clinical outcomes among left ventricular assist device recipients in the United States have been recognized. However, an investigation of the social and clinical determinants of sex-associated differences is lacking. Methods: Left ventricular assist device receiving patients enrolled in Interagency Registry for Mechanically Assisted Circulatory Support between 2005 and 2017 were included. The primary outcome was all-cause mortality. Secondary outcomes included heart transplantation and postimplantation adverse event rates. The cohort was stratified by the social subgroup of race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic), and clinical subgroups of device strategy (destination therapy, bridge to transplant, and bridge to candidacy), and implantation center volume (low [≤20 implants/y], medium [21–30 implants/y], and high [>30 implants/y]). A multivariable-adjusted Cox proportional hazard model was used to assess the risk of death and heart transplantation with prespecified interaction testing. Poisson regression was used to estimate adverse events by sex across the various subgroups. Results: Among 18 525 patients, there were 3968 (21.4%) females. Compared with their male counterparts, Hispanic (adjusted hazard ratio [HR adj ], 1.75 [1.23–2.47]) females had the highest risk of death followed by non-Hispanic White females (HR adj , 1.15 [1.07–1.25]; P interaction =0.02). Hispanic (HR adj , 0.60 [0.40–0.89]) females had the lowest cumulative incidence of heart transplantation followed by non-Hispanic Black females (HR adj , 0.76 [0.67–0.86]), and non-Hispanic White females (HR adj , 0.88 [0.80–0.96]) compared with their male counterparts ( P interaction <0.001). Compared with their male counterparts, females on the bridge to candidacy strategy (HR adj , 1.32 [1.18–1.48]) had the highest risk of death ( P interaction =0.01). The risk of death ( P interaction =0.44) and cumulative incidence of heart transplantation ( P interaction =0.40) did not vary by sex in the center volume subgroup. A higher incidence rate of adverse events after left ventricular assist device implantation was also seen in females compared with the males, overall, and across all subgroups. Conclusions: Among left ventricular assist device recipients, the risk of death, the cumulative incidence of heart transplantation, and adverse events differ by sex across the social and clinical subgroups.

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