Background Blood pressure (BP) trajectories derived from measurements repeated over years have low measurement error and may improve cardiovascular disease prediction compared to single, average, and usual BP (single BP adjusted for regression dilution). We characterized 10-year BP trajectories and examined their association with cardiovascular mortality, all-cause mortality, and life years lost. Methods and Results Data from 2 prospective and nearly extinct cohorts of middle-aged men—the Minnesota Business and Professional Men Study (n=261) and the Zutphen Study (n=632)—were used. BP was measured annually during 1947–1957 in Minnesota and 1960–1970 in Zutphen. BP trajectories were identified by latent mixture modeling. Cox proportional hazards and linear regression models examined BP trajectories with cardiovascular mortality, all-cause mortality, and life years lost. Associations were adjusted for age, serum cholesterol, smoking, and diabetes mellitus. Mean initial age was about 50 years in both cohorts. After 10 years of BP measurements, men were followed until death on average 20 years later. All Minnesota men and 98% of Zutphen men died. Four BP trajectories were identified, in which mean systolic BP increased by 5 to 49 mm Hg in Minnesota and 5 to 20 mm Hg in Zutphen between age 50 and 60. The third systolic BP trajectories were associated with 2 to 4 times higher cardiovascular mortality risk, 2 times higher all-cause mortality risk, and 4 to 8 life years lost, compared to the first trajectory. Conclusions Ten-year BP trajectories were the strongest predictors, among different BP measures, of cardiovascular mortality, all-cause mortality, and life years lost in Minnesota. However, average BP was the strongest predictor in Zutphen.