The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 recommendations include early identification of prehypertension (120 to 139 mm Hg systolic or 80 to 89 mm Hg diastolic). Although prehypertension is a risk factor for hypertension, little is known of prehypertension's independent risk for mortality. We conducted an analysis of a nationally representative cohort in the second National Health and Nutrition Examination Survey 1976 to 1980 (NHANES II) and the NHANES II Mortality Study, 1992. The cohort included 9,087 patients aged 30 to 74 years at baseline, who represented nearly 95 million Americans. Cox proportional-hazards models were conducted for both cardiovascular disease (CVD) and all-cause mortality. The unadjusted relative risk of both all-cause (hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.02 to 1.58) and CVD (HR 1.66, 95% CI 1.21 to 2.26) mortality is increased for patients with prehypertension over patients with normal blood pressure (BP). Almost all patients with hypertension (93%), prehypertension (90%), and normal BP (85%) have other CVD risk factors. When the presence of any CVD risk factor is adjusted for in the survival analysis, the adjusted relative risk of both all-cause (HR 0.82, 95% CI 0.64 to 1.04) and CVD (HR 1.00, 95% CI 0.72 to 1.39) mortality is no longer increased for patients with prehypertension. Similarly, in analyses of patients aged >/=55 years, there is no significant independent mortality risk for prehypertension. Lifestyle interventions targeting multiple risk factors including BP may be the most effective prevention strategy.