BACKGROUND: Increased attention has been given to pulse pressure (PP) as a potential independent risk factor for cardiovascular disease (CVD). We examined the relationship between the three indices of blood pressure consisting of systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP (= SBP - DBP), respectively, and incident acute coronary heart disease (CHD). METHODS: Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study, a national cohort study of 30,239 black and white participants > 45 years of age, were enrolled between 2003 and 2007. The participants' SBP, DBP, and PP values were separated into the four groups of < 45mm Hg, 45-54.9mm Hg, 55-64.9mm Hg, and ≥ 65mm Hg, and were analyzed on a groupwise basis. Reported CHD events were confirmed by expert adjudication. Cox proportional hazards models were used to examine the association of incident CHD (first acute CHD event) for the four groups of BP measurements with multivariate-adjusted sociodemographic and clinical risk factors. RESULTS: Analyses were done for 22,909 men and women (40.4% black, 44.6% male) ≥ 45 years of age (mean age = 64.7±9.4 years) without prevalent CHD at baseline. Associations were found for 681 CHD events, over a mean 3.4 years of follow-up (maximum 6 years), with each unadjusted PP group (hazard ratio [HR] with 95% confidence limits for PP of 45-54.9mm Hg, 55-64.9mm Hg, and ≥ 65mm Hg, respectively, of 3.82, 3.08, and 4.73 as compared with PP < 45mm Hg; P < 0.0001 for linear trend), and this persisted after full adjustment, including that for SBP (1.50, 1.08, 2.09; P trend < 0.01). Subgroup analyses showed no statistically significant differences across age, race, or region of the country, but did suggest the possibility that men were more sensitive to PP than were women. CONCLUSIONS: Pulse pressure is positively and independently (particularly so with regard to independence from SBP) associated with incident CHD, and there were no significant racial or regional differences in this association.