PURPOSE: Prior studies have observed higher mortality in women after LVAD; however a paucity of data exists on mediators of observed disparities. We used the International Registry for Mechanically Assisted Circulatory Support (IMACS) database to examine what clinical factors might mediate observed gender differences in mortality after LVAD. METHODS: We analyzed 15,498 adults (>18 years) who received a CF LVAD from Jan 2013 - Sep 2017 (age: 56.0 ± 13.2 yrs, 20.8% female, 35.9% centrifugal pumps, median follow-up:13.4 [IQR 5.6, 25.9] months). Inverse probability weighted Cox proportional hazards model was used to estimate the association of female gender with all-cause mortality. Covariates included age, BSA, pump type, sodium, BUN, bilirubin, INR, hemoglobin, eGFR, MELD score, modified HeartMate II Risk Score (without center volume), INTERMACS profile, PADP and CI. Restricted cubic spline regression analysis was used to examine hazard ratio (HR) variation with time. Causal mediation analysis was performed to test plausible pre-implant mediators that were significantly different between genders (p<0.05). RESULTS: Women were younger, less likely to have ischemic HF, and more likely to have a centrifugal pump (all p<0.001). Women had higher mortality after LVAD (adjusted HR: 1.38, 95% CI: 1.20 - 1.57, p<0.001). Gender*time interaction was significant (p<0.001), with women experiencing increased mortality during the first 3 months after implant (adj HR: 1.76, 95% CI: 1.42 - 2.19, p<0.001), but not after (adj HR: 1.17, 95% CI: 0.98-1.39, p=0.08). Increased tricuspid regurgitation (TR), and smaller LV end-diastolic diameter (LVEDD) at baseline mediated ∼20.6% of the increased early hazard of death in females; however most of the mechanisms underlying the increased hazard remained unexplained. CONCLUSION: Women have higher post-LVAD mortality during the first 3 months after implant, that is partly mediated by increased TR and smaller LVEDD at baseline. Further studies are needed to explore additional underlying mechanisms.