Elevated blood pressure (BP) remains the leading cause of mortality globally, and efforts to control it have been disappointing. Meta-analyses of antihypertensive randomized controlled trials reveal a near-exact reversal of the BP-related risks identified in cohort studies. For an observed increase in cardiovascular disease risk of 12.5%, 25%, 50%, and 75% with a 5, 10, 20, or 40 mm Hg higher level of BP, respectively, the corresponding BP reductions in antihypertensive randomized controlled trial meta-analyses document a reversal of risks by 7%, 17% of 22%, 54%, and 64%, respectively, providing almost perfect mathematical concordance between the observed and expected benefit of antihypertensive treatment. Treatment benefits have been demonstrated across a wide range of baseline BPs and in individuals with and without prior established cardiovascular disease. Meta-analyses of antihypertensive treatment randomized controlled trials also indicate that the treatment benefits far outweigh any potential risks for adverse effects. The mathematical evidence of the effectiveness of BP-lowering in reducing the incidence of BP-related cardiovascular disease without imposing relevant adverse effects should be considered by clinicians and guideline committees in defining the diagnosis of hypertension and establishing antihypertensive treatment goals. Setting lower BP values for the diagnosis and treatment of hypertension could yield a substantial reduction in the global burden of disease due to high BP.