Abstract Cardiovascular disease (CVD) causes a high disease burden. Physical activity (PA) reduces CVD morbidity and mortality. We aimed to determine the relationship between the composition of moderate-to-vigorous PA (MVPA), light PA (LPA), sedentary behavior (SB), and sleep during midlife to the incidence of major adverse cardiac events (MACE) and all-cause mortality at a 7-year follow-up. The study population consisted of Northern Finland Birth Cohort 1966 members who participated in the 46-year follow-up in 2012 and were free of MACE (N = 4147). Time spent in MVPA, LPA, and SB was determined from accelerometer data. Sleep time was self-reported. Hospital visits and deaths were obtained from national registers. Participants were followed until December 31, 2019, or first MACE occurrence (acute myocardial infarction, unstable angina pectoris, stroke, hospitalization due to heart failure, or death due to CVD), death from another cause, or censoring. Cox proportional hazards model was used to estimate hazard ratios of MACE incidence and all-cause mortality. Isotemporal time reallocations were used to demonstrate the dose–response association between time spent in behaviors and outcome. The 24-h time composition was significantly associated with incident MACE and all-cause mortality. More time in MVPA relative to other behaviors was associated with a lower risk of events. Isotemporal time reallocations indicated that the greatest risk reduction occurred when MVPA replaced sleep. Higher MVPA associates with a reduced risk of incident MACE and all-cause mortality after accounting for the 24-h movement composition and confounders. Regular engagement in MVPA should be encouraged in midlife.