Plasma renin activity (PRA) may be a surrogate for vascular damage. The authors hypothesize that PRA is associated with cardiovascular and cerebrovascular disease (CED). A cross-sectional study (January 1, 1998, to December 31, 2009) was performed on hypertensive individuals 18 years and older using multivariable logistic regression models to estimate odds ratios (ORs) for ischemic heart disease (IHD), congestive heart failure (CHF), and CED based on PRA quartiles controlling for age, sex, race, diabetes mellitus (DM), and medication use. Among 7887 individuals (60% women; 34% whites, 23% blacks, and 19% Hispanics; and 29% with DM), the adjusted ORs (95% CI) for IHD were 0.94 (0.80–1.10), 1.09 (0.92–1.29), and 1.18 (1.00–1.39); for CHF were 1.23 (0.99–1.53), 1.27 (1.01–1.61), and 1.41 (1.13–1.77); and for CED were 0.95 (0.78–1.17), 0.77 (0.61–0.97), and 0.97 (0.78–1.20) for the second, third, and fourth quartiles compared with the first quartile. Higher PRA was associated with greater likelihood for prevalent IHD and CHF but not CED in this large ethnically diverse population of hypertensive individuals.