There is a paucity of data regarding the sex-related differences in the trends and outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR). The Nationwide Readmissions Database (2015-2018) was queried for admissions for TS-TMVR. Propensity matched analysis was conducted to compare outcomes with hospitalizations for TS-TMVR among women versus men. The main study outcome was in-hospital mortality. Our final analysis included 2063 hospitalizations for TS-TMVR; of whom, 58.1% were women. The proportion of women among those undergoing TS-TMVR increased from 50% in 2015 to 60.2% in 2018 (Ptrend = 0.04). Compared with men, women undergoing TS-TMVR were slightly younger, and had a distinct profile of comorbidities. After matching, there was no significant difference in in-hospital mortality among women versus men undergoing TS-TMVR (7.8% vs. 6.1%, OR = 1.30; 95% CI: 0.79-2.13). Subgroup analyzes showed an interaction toward higher mortality with women versus men among patients with CKD (Pinteraction = 0.07). There were no significant differences between women and men in in-hospital complications or length of stay after TS-TMVR. Compared with men, women undergoing TS-TMVR were more likely to be discharged to a nursing facility (17.7% vs. 11.5%, p = 0.01) and had higher rates of 30-day readmissions (22.4% vs. 13.6%, p = 0.01). This nationwide analysis showed an increase in the proportion of women among patients undergoing TS-TMVR during the study years. There were no differences in in-hospital mortality, in-hospital complications, or length of stay between both sexes following TS-TMVR. Women were more likely to be discharged to nursing facilities and had higher rates of readmission at 30 days even after propensity matching.