The Seventh Report of the Joint National Commission (JNC 7) on High Blood Pressure established prehypertension (120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic) as a new risk category. We aim to determine the risk of major cardiovascular events associated with blood pressure in the prehypertensive range in a longitudinal, population-based cohort.Analyses were conducted on participants in the National Health and Nutrition Examination Survey I (1971-1975) observed for 18 years for major cardiovascular disease events. Cox proportional hazard ratios were calculated to assess relative risk of cardiovascular disease, including stroke, myocardial infarction, and heart failure, in participants with prehypertension and normal blood pressure (<120/80 mm Hg).Prehypertension was associated with increased risk for cardiovascular disease (1.79 [95% confidence interval (CI) 1.40-2.24]) in unadjusted analysis. After adjustment for cardiovascular risk factors, the relationship of prehypertension to cardiovascular disease was diminished but persisted (1.32 [95% CI 1.05-1.65]). Ninety-three percent of prehypertensive individuals had at least 1 cardiovascular risk factor. Low prehypertension (120-129/80-84 mm Hg) was associated with increased cardiovascular disease in unadjusted analyses (1.56 [95% CI 1.23-1.98]) but was not statistically significant in adjusted analyses (1.24 [95% CI 0.96-1.59]). High-normal blood pressure (130-139/85-89 mm Hg) remained a predictor of cardiovascular disease in unadjusted (2.13 [95% CI 1.64-2.76]) and adjusted (1.42 [95% CI 1.09-1.84]) analyses.In a longitudinal, population-based, US cohort, prehypertension was associated with increased risk of major cardiovascular events independently of other cardiovascular risk factors. These findings, along with the presence of cardiovascular risk factors in the majority of participant sample with prehypertension, support recommendations for physicians to actively target lifestyle modifications and multiple risk reduction in their prehypertensive patients.