The effect of elevated blood pressure on risk of cardiovascular and renal disease has been documented in both observational epidemiologic studies and clinical trials. However, these studies have traditionally concentrated on diastolic blood pressure to characterize the risk associated with hypertension. We reviewed evidence from prospective studies and randomized controlled trials to quantify the risk associated with systolic blood pressure. Prospective studies and randomized controlled clinical trials that were published in English-language journals were retrieved using MEDLINE, bibliographies, and the authors’ reference files. All retrieved publications were reviewed and information on sample size, duration, study design, antihypertensive medication, participant characteristics, and outcomes was abstracted for randomized controlled trials that reported systolic blood pressure reduction during intervention. Several prospective studies indicate that the association between systolic blood pressure and risk of coronary heart disease, stroke, and end-stage renal disease is continuous, graded, and independent. Furthermore, they suggest that the association of systolic blood pressure with these outcomes is stronger than that of diastolic blood pressure. Pooling of the data available from randomized controlled trials indicates that an average reduction of 12 to 13 mm Hg in systolic blood pressure over 4 years of follow-up is associated with a 21% reduction in coronary heart disease, 37% reduction in stroke, 25% reduction in total cardiovascular mortality, and 13% reduction in all-cause mortality rates. These data indicate that systolic blood pressure is an independent and strong predictor for risk of cardiovascular and renal disease. (Am Heart J 1999;138:S211-S219.)