ABSTRACT: Background Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease and is associated with significant mortality and morbidity. Contemporary data comparing the sex differences in trends, revascularization strategies, and in-hospital outcomes among patients with CLI are scarce. Methods and Results Using the National Inpatient Sample database years 2002 to 2015, we identified hospitalizations for CLI. Temporal trends for hospitalizations for CLI were evaluated. The differences in demographics, revascularization, and in-hospital outcomes between both sexes were compared. Among 2 400 778 CLI hospitalizations, 43.6% were women. Women were older and had a higher prevalence of obesity, hypertension, heart failure, and prior stroke. Women were also less likely to receive any revascularization (34.7% versus 35.4%, P<0.001), but the trends of revascularization have been increasing among both sexes. Revascularization was associated with lower in-hospital mortality among women (adjusted odds ratio [OR], 0.76; 95% CI, 0.71-0.81) and men (adjusted OR, 0.69; 95% CI, 0.65-0.73). On multivariable analysis adjusting for patient- and hospital-related characteristics as well as revascularization, women had a higher incidence of in-hospital mortality, postoperative hemorrhage, need for blood transfusion, postoperative infection, ischemic stroke, and discharge to facilities compared with men. Conclusions In this nationwide contemporary analysis of CLI hospitalizations, women were older and less likely to undergo revascularization. Women had a higher incidence of in-hospital mortality and bleeding complications compared with men. Sex-specific studies and interventions are needed to minimize these gaps among this high-risk population.