Rationale: Data are limited regarding the influence of life-course cumulative burden of increased body mass index (BMI) and elevated blood pressure on the progression of left ventricular (LV) geometric remodeling in midlife. Objective: To investigate the dynamic changes in LV mass and LV geometry over 6.4 years during midlife and to examine whether the adverse progression of LV geometric remodeling is influenced by the cumulative burden of BMI and blood pressure from childhood to adulthood. Methods and Results: The study consisted of 877 adults (604 whites and 273 blacks; 355 males; mean age=41.4 years at follow-up) who had 5-15 examinations of BMI and blood pressure from childhood and 2 examinations of LV dimensions at baseline and follow-up 6.4 years apart during adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI and systolic blood pressure (SBP). After adjusting for age, race, sex, smoking, alcohol drinking and baseline LV mass index, the annual increase rate of LV mass index was associated with all BMI measures (β=0.16-0.36, P<0.05 for all), adult SBP (β=0.07, P=0.04), and total AUC of SBP (β=0.09, P=0.01), but not with childhood and incremental AUC values of SBP. All BMI and SBP measures (except childhood SBP) were significantly associated with increased risk of incident LV hypertrophy, with odds ratios (ORs) of BMI (OR=1.85-2.74, P<0.05 for all) being significantly greater than those of SBP (OR=1.09-1.34, P<0.05 for all except childhood SBP). In addition, all BMI measures were significantly and positively associated with incident eccentric and concentric LV hypertrophy. Conclusions: Life-course cumulative burden of BMI and blood pressure is associated with the development of LVH in midlife, with BMI showing stronger associations than blood pressure.