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Several studies have shown sex differences in acute coronary syndromes (ACS), but their understanding is far from complete. Thus, the study aims to evaluate sex differences in management and outcomes of unselected patients with ACS.From 22 April 2009 to 29 December 2010, 6394 consecutive patients with ACS (44.7% ST-elevation myocardial infarction) were prospectively enrolled and followed for 6 months. Women (N = 1894, 29.6%) were older, had more comorbidities, and worse clinical presentation than men. Fewer women underwent reperfusion [68.0% women vs. 84.1% men, P < 0.0001, adjusted odds ratio (OR): 0.53, 95% confidence interval (CI): 0.43–0.66] in ST-elevation myocardial infarction, and coronary angiography during hospitalization (72.2% women vs. 81.1% men, P < 0.0001, adjusted OR: 0.70, 95% CI: 0.57–0.85) in no-ST-elevation ACS. Women had worse outcomes than men during hospitalization, and at 6-month follow-up. At multivariable analysis, female sex was significantly associated with a higher risk of in-hospital Thrombolysis in Myocardial Infarction major bleedings (OR: 1.80, 95% CI: 1.09–2.96, P = 0.02), but not of 6-month death.Women with ACS in clinical practice present a clustering of high-risk features that may contribute to their worse outcomes as compared with men, although female sex is not an independent predictor of death at 6-month follow-up.