© 2018 American Society of Echocardiography Background: The aim of this study was to determine whether long-term patterns of change in adiposity throughout young adulthood are associated with systolic and diastolic function in midlife. Methods: Participants in the Coronary Artery Risk Development in Young Adults study, a multicenter, population-based cohort, underwent repeated anthropometric assessment (body mass index [BMI], waist circumference, and waist-to-hip ratio) from examination years 0 to 25. At year 25, longitudinal, circumferential, and radial strain and tissue Doppler velocities were assessed by echocardiography. Group-based trajectory modeling was used to identify 25-year trajectories of change in anthropometric measures and to examine associations between trajectories of adiposity change and indices of cardiac mechanics. Results: Among 3,310 participants, four distinct trajectories of BMI change were identified: stable BMI (36% of the cohort; mean ΔBMI, 1.6 kg/m2), mild increase (40%; mean ΔBMI, 6.0 kg/m2), moderate increase (18%; mean ΔBMI, 10.8 kg/m2), and major increase (6%; mean ΔBMI, 15.5 kg/m2). Trajectories of greater BMI increase were associated with lower adjusted e′ velocity and higher E/e′ ratio compared with the stable BMI group, independent of year 0 or year 25 BMI. Participants in increasing BMI trajectory groups compared with the stable BMI group had lower absolute longitudinal strain and greater odds of diastolic dysfunction, independent of year 0 BMI but not year 25 BMI. Similar patterns were observed for change in waist circumference and waist-to-hip ratio trajectory groups. Conclusions: Steeper trajectories of BMI increase from young adulthood to middle age, a vulnerable period for weight gain, are independently associated with lower e′ velocity and higher E/e′ ratio, but not systolic dysfunction, in midlife.