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Current knowledge of the impact of cardiovascular risk factors in Latin America is limited.As part of the INTERHEART study, 1237 cases of first acute myocardial infarction and 1888 age-, sex-, and center-matched controls were enrolled from Argentina, Brazil, Colombia, Chile, Guatemala, and Mexico. History of smoking, hypertension, diabetes mellitus, diet, physical activity, alcohol consumption, psychosocial factors, anthropometry, and blood pressure were recorded. Nonfasting blood samples were analyzed for apolipoproteins A-1 and B-100. Logistic regression was used to estimate multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Persistent psychosocial stress (OR, 2.81; 95% CI, 2.07 to 3.82), history of hypertension (OR, 2.81; 95% CI, 2.39 to 3.31), diabetes mellitus (OR, 2.59; 95% CI, 2.09 to 3.22), current smoking (OR, 2.31; 95% CI, 1.97 to 2.71), increased waist-to-hip ratio (OR for first versus third tertile, 2.49; 95% CI, 1.97 to 3.14), and increased ratio of apolipoprotein B to A-1 (OR for first versus third tertile, 2.31; 95% CI, 1.83 to 2.94) were associated with higher risk of acute myocardial infarction. Daily consumption of fruits or vegetables (OR, 0.63; 95% CI, 0.51 to 0.78) and regular exercise (OR, 0.67; 95% CI, 0.55 to 0.82) reduced the risk of acute myocardial infarction. Abdominal obesity, abnormal lipids, and smoking were associated with high population-attributable risks of 48.5%, 40.8%, and 38.4%, respectively. Collectively, these risk factors accounted for 88% of the population-attributable risk.Interventions aimed at decreasing behavioral risk factors, lowering blood pressure, and modifying lipids could have a large impact on the risk of acute myocardial infarction among Latin Americans.