Using epidemiological and clinical trial evidence, the sixth report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure (JNC-VI) updated previous guidelines to suggest that in addition to blood pressure, decisions on initial treatment should emphasize absolute cardiovascular disease risk. We estimated the impact of using cardiovascular disease risk on treatment recommendations for the US population using data from 16 527 participants in the Third National Health and Nutrition Examination Survey. In the US population > or =20 years of age, 36% (62 million) had high-normal blood pressure or greater (systolic/diastolic blood pressure > or =130 mm Hg/> or =85 mm Hg) or were taking antihypertensive medication. Of this population, 5.1% (3.2 million) were stratified into risk group A (no cardiovascular disease risk factors or prevalent cardiovascular disease), 66.3% (41.4 million) into risk group B (> or =1 major risk factor), and 28.6% (17.9 million) into risk group C (diabetes mellitus, clinical cardiovascular disease, target organ damage). Also, 26% of this group (16.2 million) had high-normal blood pressure and were in risk groups A or B, a context in which vigorous lifestyle modification is recommended in the JNC-VI guidelines. Additionally, 11% (7.0 million) had high-normal blood pressure (systolic/diastolic, 130 to 139 mm Hg/85 to 89 mm Hg, respectively) or stage-1 hypertension (140 to 159 mm Hg/90 to 99 mm Hg), and at least 1 factor, placing them in risk group C, but they were not currently on antihypertensive medication. JNC-VI, but not previous JNC guidelines, specifically recommends drug therapy as initial treatment for these patients. We conclude that JNC-VI refines cardiovascular risk and enfranchises more Americans to undertake more aggressive risk reduction maneuvers.