The heart progressively remodels over the life course, yet longitudinal data characterizing such remodeling in the community are limited. Using multilevel modeling, we analyzed up to 4 serial echocardiographic observations obtained over a 16-year period in 4062 Framingham Heart Study participants (mean age 45 years, 54% women; 11 485 person-observations). We related left ventricular (LV) wall thickness, LV systolic and diastolic dimensions, and fractional shortening to age, sex, body mass index, blood pressure (including antihypertensive medication use), smoking, and diabetes mellitus (separate analyses for each echocardiographic measure). With advancing age, LV dimensions decreased, whereas fractional shortening and LV wall thickness increased concomitantly. Male sex, body mass index, and blood pressure indices/hypertension treatment were significantly related to both greater LV dimensions and LV wall thickness. The effect of age on cardiac remodeling was influenced by key covariates (P<0.05 for all interactions): Women and individuals with diabetes mellitus experienced greater age-associated increases in LV wall thickness; presence of diabetes or a higher blood pressure was associated with a lesser decrease in LV diastolic dimensions with increasing age; and antihypertensive medication use was a marker of an attenuated increase in fractional shortening with aging. Cardiac remodeling over the adult life course is characterized by a distinct pattern of increasing LV wall thickness, decreasing LV dimensions, and increasing fractional shortening with advancing age. Overall, female sex, greater blood pressure load, and presence of diabetes mellitus serve to attenuate this remodeling pattern. These observations suggest a mechanism for the preponderance of women with hypertension and individuals with diabetes among patients with diastolic heart failure.