Left ventricular (LV) mass and the LV ejection fraction (LVEF) are major independent predictors of future cardiovascular disease. The association of LV mass with the future LVEF in younger populations has not been studied. The aim of this study was to investigate the relation of LV mass index (LVMI) at ages 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CARDIA is a longitudinal study that enrolled young adults in 1985 and 1986. In this study, participants with echocardiographic examinations at years 5 and 25 were included. LVMI and the LVEF were assessed using M-mode echocardiography at year 5 and using M-mode and 2-dimensional imaging at year 25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year 25 was 62%. Although there was no cross-sectional correlation between LVMI and the LVEF at year 5, there was a small but statistically significant negative correlation between LVMI at year 5 and the LVEF 20 years later (r = -0.10, p <0.0001); this inverse association persisted for LVMI in the multivariate model. High LVMI was an independent predictor of systolic dysfunction (LVEF <50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, LVMI in young adulthood in association with chronic risk exposure affects systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought. © 2014 Elsevier Inc. All rights reserved.