Background Few data exist on the long-term risk prediction of elevated left ventricular (LV) mass quantified by MRI for cardiovascular (CV) events in a contemporary, ethnically diverse cohort. Purpose To assess the long-term impact of elevated LV mass on CV events in a prospective cohort study of a multiethnic population in relationship to risk factors and coronary artery calcium (CAC) score. Materials and Methods The Multi-Ethnic Study of Atherosclerosis, or MESA (ClinicalTrials.gov: NCT00005487), is an ongoing prospective multicenter population-based study in the United States. A total of 6814 participants (age range, 45-84 years) free of clinical CV disease at baseline were enrolled between 2000 and 2002. In 4988 participants (2613 [52.4%] women; mean age, 62 years ± 10.1 [standard deviation]) followed over 15 years for CV events, LV mass was derived from cardiac MRI at baseline enrollment by using semiautomated software at a central core laboratory. Cox proportional hazard models, Kaplan-Meier curves, and z scores were applied to assess the impact of LV hypertrophy. Results A total of 290 participants had hard coronary heart disease (CHD) events (207 myocardial infarctions [MIs], 95 CHD deaths), 57 had other CV disease-related deaths, and 215 had heart failure (HF). LV hypertrophy was an independent predictor of hard CHD events (hazard ratio [HR]: 2.7; 95% confidence interval [CI]: 1.9, 3.8), MI (HR: 2.8; 95% CI: 1.8, 4.0), CHD death (HR: 4.3; 95% CI: 2.5, 7.3), other CV death (HR: 7.5; 95% CI: 4.2, 13.5), and HF (HR: 5.4; 95% CI: 3.8, 7.5) (P < .001 for all end points). LV hypertrophy was a stronger predictor than CAC for CHD death, other CV death, and HF (z scores: 5.4 vs 3.4, 6.8 vs 2.4, and 9.7 vs 3.2 for LV hypertrophy vs CAC, respectively). Kaplan-Meier analysis demonstrated an increased risk of CV events in participants with LV hypertrophy, particularly after 5 years. Conclusion Elevated left ventricular mass was strongly associated with hard coronary heart disease events, other cardiovascular death, and heart failure over 15 years of follow-up, independent of traditional risk factors and coronary artery calcium score. © RSNA, 2019 See also the editorial by Hanneman in this issue.