Although the variability of cardiovascular disease mortality by geography, race, and sex is well known, less is known about risk factor variation. We assessed 20-year incidence of hypertension, a cardiovascular disease risk factor, across 4 US urban areas and by race-sex. Among 3436 eligible adults 18 to 30 years of age when recruited in 1985 to 1986 in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) cohort, we examined 20-year cumulative incidence of hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg or antihypertensive medication use at any examination) by site and race-sex, adjusting for baseline and time-dependent covariates with Cox regression. Twenty-year incidence, when the mean age was ≈ 45 years, was 34.5% in black men (n = 617), 37.6% in black women (n = 965), 21.4% in white men (n = 856), and 12.3% in white women (n = 998; P<0.001). Incidence was 33.6% in Birmingham, Ala, 23.4% in Chicago, Ill, 19% in Minneapolis, Minn, and 27.4% in Oakland, Calif (P<0.001). After adjustment for age, race, sex, heart rate, body mass index, smoking, family history, education, uric acid, alcohol use, physical activity, and baseline systolic blood pressure, hazard ratios (95% CI) compared with Birmingham were 0.72 (0.59 to 0.87) for Chicago, 0.60 (0.50 to 0.74) for Minneapolis, and 0.73 (0.61 to 0.87) for Oakland. Race-sex differences persisted after adjustment for site, especially for black women. From young adulthood to middle age, hypertension incidence varies significantly across urban areas. Independent of geography, blacks, especially women, are at markedly higher risk of hypertension. Hypertension incidence may contribute to geographic and racial differences in cardiovascular disease mortality, including stroke.