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Objectives: The purpose of this research was to determine if sex and gender differences in the management of acute coronary syndromes (ACS) are associated with differences in prognosis after ACS. Background: Previous investigators have reported sex/gender differences in the management of patients with ACS, but the impact of these differences on prognosis is unclear. Methods: We analyzed data from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, which enrolled 4,836 women and 7,726 men with ACS. Patients were classified into risk strata using the Thrombolysis In Myocardial Infarction (TIMI) score. Results: Women underwent fewer invasive procedures including angiography, angioplasty, and coronary artery bypass graft (CABG) surgery (47.6% vs. 60.5%; p = 0.0001) compared to men. No significant differences in cardiovascular death, myocardial infarction (MI), or stroke were observed (9.8% vs. 10.9%; p = 0.04), although women were more likely than men to develop refractory ischemia and to be rehospitalized for chest pain during follow-up (16.6% vs. 13.9%; p = 0.0001). These differences were particularly evident among TIMI high-risk women. A significant interaction between TIMI risk and gender for the outcome of refractory angina and rehospitalization for angina was present. Conclusions: Compared to men, high-risk women with ACS undergo less coronary angiography, angioplasty, and CABG surgery, and while they do not have higher incidence cardiovascular death, recurrent MI, or stroke, they suffer an increased rate of refractory ischemia and rehospitalization. All high-risk women and men with ACS should receive optimal medical management, and be considered for coronary angiography with possible revascularization if their coronary anatomy warrants it. [Copyright &y& Elsevier]