Insufficient moderate-to-vigorous-intensity physical activity (MVPA) and high volumes of sedentary time (ST) have both been associated with increased risk of all-cause mortality, cardiovascular disease (CVD), and some cancers1. However, epidemiological evidence has mostly relied on self-reported physical activity (PA) measures, which are prone to reporting bias and measurement error. Cohort studies incorporating objective assessments of PA are emerging2-4; but few investigate relationships of accelerometer-measured PA and ST with clinical endpoints, particularly incident CVD, and include both men and women5. Additionally, the relevance of light-intensity physical activity (LIPA) in this context, which is an important contributor to total physical activity and may be a more feasible target for middle-to-older aged adults, remains unclear. Here, we examine the prospective associations of accelerometer-measured PA and ST with incident CVD (primary outcome), incident cancer, and all-cause mortality.