BACKGROUND—The association of overall diet, as characterized by dietary patterns, with risk of incident acute coronary heart disease (CHD) has not been studied extensively in samples including sociodemographic and regional diversity. METHODS AND RESULTS—We used data from 17 418 participants in Reasons for Geographic and Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal study of white and black adults aged ≥45 years, enrolled from 2003 to 2007. We derived dietary patterns with factor analysis and used Cox proportional hazards regression to examine hazard of incident acute CHD events – nonfatal myocardial infarction and acute CHD death – associated with quartiles of consumption of each pattern, adjusted for various levels of covariates. Five primary dietary patterns emergedConvenience, Plant-based, Sweets, Southern, and Alcohol and Salad. A total of 536 acute CHD events occurred over a median (interquartile range) 5.8 (2.1) years of follow-up. After adjustment for sociodemographics, lifestyle factors, and energy intake, highest consumers of the Southern pattern (characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages) experienced a 56% higher hazard of acute CHD (comparing quartile 4 with quartile 1hazard ratio, 1.56; 95% confidence interval, 1.17–2.08; P for trend across quartiles=0.003). Adding anthropometric and medical history variables to the model attenuated the association somewhat (hazard ratio, 1.37; 95% confidence interval, 1.01–1.85; P=0.036). CONCLUSIONS—A dietary pattern characteristic of the southern United States was associated with greater hazard of CHD in this sample of white and black adults in diverse regions of the United States.