Nearly 20% of older adults are at high risk of heart disease and stroke from untreated isolated systolic hypertension (ISH). Long-term follow-up of the Pittsburgh cohort of the Systolic Hypertension in the Elderly Program (SHEP) revealed cardiovascular event rate estimates of 58% and 79% for the active and placebo groups, respectively (P = .001). Compared with normotensive controls, the relative risk of an event was 1.6 (95% confidence interval, 1.1-2.4) for ISH participants assigned to active treatment and 3.0 (95% confidence interval, 2.1-4.4) for the placebo group. Treatment of ISH in older adults results in reduced long-term (14 years) event rates. The authors conclude that treatment before advanced atherosclerosis develops will likely produce the best long-term outcome.