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Although the World Health Organization has recommended moderate- to vigorous-intensity physical activity (MVPA) to prevent cardiovascular disease (CVD) and some cancers, there are no estimates of lifetime risk of these noncommunicable diseases according to PA levels. We aimed to estimate the lifetime risk of CVD and cancers according to PA levels.We followed 5807 men and 7252 women in the United States, 45–64 yr old, initially free of CVD and cancer from 1987 through 2012, and used a life table approach to estimate lifetime risks of CVD (coronary heart disease, heart failure, and stroke) and total cancer according to PA levels: poor (0 min·wk−1 of MVPA), intermediate (1–74 min·wk−1 of VPA or 1–149 min·wk−1 of MVPA), or recommended (≥75 min·wk−1 of VPA or ≥150 min·wk−1 of MVPA).During the 246,886 person-years of follow-up, we documented 4065 CVD and 3509 cancer events and 2062 non-CVD and 2326 noncancer deaths. In men, the lifetime risks of CVD from 45 through 85 yr were 52.7% (95% confidence interval = 49.4–55.5) for poor PA and 45.7% (42.7–48.3) for recommended PA. In women, the respective lifetime risks of CVD were 42.4% (39.5–44.9) and 30.5% (27.5–33.1). Lifetime risks of total cancer were 40.1% (36.9–42.7) for poor PA and 42.6% (39.7–45.2) for recommended activity in men and 31.4% (28.7–33.8) and 30.4% (27.7–32.9), respectively, in women.Compared with a poor PA level, the PA recommended by the World Health Organization was associated with lower lifetime risk of CVD, but not total cancer, in both men and women.