Context.-Mortality after acute myocardial infarction is worse in women than in men, even after adjustment for comorbidity and age dissimilarities between sexes. Objective.-To assess the influence of sex on survival after acute myocardial infarction. Design.-Inception cohort obtained in a prospective registry of patients with acute myocardial infarction from 1992 through 1994. Setting.-Four teaching hospitals in northeastern Spain. Patients.-All consecutive patients aged 80 years or younger with first acute myocardial infarction. A total of 331 women and 1129 men were included. Main Outcome Measure.-Survival at 28 days and mortality or readmission at 6 months. Results.-Women were older (mean, 68.6 vs 60.1 years), presented more often with diabetes (52.9% vs 23.3%), hypertension (63.9% vs 42.3%), or previous angina (44.6% vs 37.4%), and developed more severe myocardial infarctions than men (acute pulmonary edema or cardiogenic shock occurred in 24.8% of women and 10.5% of men) (all PϽ.02). Men were more likely than women to receive thrombolytic therapy (41.3% vs 23.9%; PϽ.001), but rates of percutaneous transluminal angioplasty and coronary artery bypass graft surgery at 28 days were similar among men and women. The 28-day mortality rate was significantly higher among women (18.5% for women, 8.3% for men; PϽ.001). Revascularization procedures at 6 months were performed in a similar proportion of women and men. However, women had higher 6-month mortality rates (25.8% in women, 10.8% in men; PϽ.001) and readmission rates (23.3% for women, 12.2% for men; PϽ.001). After adjustment, women had greater risk of death than men at 28 days (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.12-2.65) and at 6 months (OR, 1.73; 95% CI, 1.18-2.52). Conclusions.-In this study population, women experienced more lethal and severe first acute myocardial infarction than men, regardless of comorbidity, age, or previous angina.