Abstract Background There is uncertainty regarding whether female sex is an independent predictor of adverse outcomes in acute coronary syndromes (ACS). Purpose We sought to describe and compare ischemic and bleeding outcomes between men and women with Non–ST-segment–Elevation (NSTE) ACS enrolled in the large Treatment of Acute coronary syndromes with Otamixaban (TAO) trial in which antithrombotic treatment was standardized and a systematic invasive approach was performed. Methods The TAO trial randomized moderate to high-risk NSTE-ACS patients with diagnostic coronary angiography planned in the first 72 hours to heparin plus eptifibatide versus otamixaban. This post-hoc analysis describes ischemic (all-cause death, new myocardial infarction, stent thrombosis within 180 days of randomization) and bleeding outcomes (TIMI major and minor bleeding within 30 days of randomization) according to sex. Results Of 13,229 patients with NSTE-ACS randomized in 55 countries, 3,980 (30.1%) were female and 9,249 (69.9%) were male. Mean age was 64.8±11.0 and 60.7±11.1 years, respectively. The prevalence of diabetes (34.0% vs. 25.8%), hypertension (80.8% vs. 67.0%), and hypercholesterolemia (55.9% vs. 52.2%) was higher among women compared with men but current smoking (21.5% vs. 38.7%) and history of previous MI were more frequent in males (15.5% vs. 20.7%). Females experienced a higher incidence of both ischemic outcomes (10.2% vs. 9.1%; OR=1.15; 95% CI, 1.01–1.30; p=0.034) and bleeding events (4.1% vs. 3.4%; OR=1.23; 95% CI, 1.02–1.49; p=0.029). Bleeding risk and CV death were particularly increased in women younger than 50 years, compared to males of the same age, at 5.5% vs. 1.4% (OR=4.00; 95% CI, 2.13–7.69; p=0.034) and 1.7% vs. 0.5% (OR=4.35; 95% CI, 1.02–20.00; p=0.02), respectively. No difference in either outcome was found between women and men between 50 and 80 years old. Above 80 years, women experienced a lower rate of bleeding (3.9% vs. 7.8%; OR=0.47; 95% CI, 0.23–0.88; p=0.024) but a similar rate of in ischemic events (16.0% vs. 17.2%; OR=0.92; 95% CI, 0.63–1.33; p=0.67). After adjustment for age, body weight, diabetes mellitus, prior PCI, serum creatinine, presenting systolic blood pressure, elevated biomarker at presentation, heart failure, the risk of ischemic (OR=1.03; 95% CI, 0.89–1.18; p=0.71) and bleeding events (OR=1.05; 95% CI, 0.85–1.33; p=0.65) were similar between men and women. Conclusions In this large international randomized trial of NSTE-ACS with standardized invasive management, women (particularly those younger than 50 years) experienced higher risks of ischemic and bleeding events than men, but the difference was not sustained after adjustment. In this population, sex was not an independent predictor of adverse outcomes in NSTE-ACS. The type of ACS (NSTE-ACS) and routine invasive management in women and men may explain this absence of difference. Acknowledgement/Funding The TAO trial was sponsored and funded by SANOFI. The present analysis was supported by the RHU iVASC grant “#ANR-16-RHUS-00010”