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Background —Angiotensin (Ang) II, a major regulatory factor for left ventricular mass, is generated from Ang I by ACE. ACE levels are associated with an insertion/deletion (I/D) polymorphism in the ACE gene. The ACE polymorphism should result in varied Ang II concentrations and hence affect left ventricular mass. We therefore investigated whether ACE genotype is a predictor of heart weight. Methods and Results —From 693 consecutive patients autopsied between 1994 and 1998 in our hospital, patients with valvular disease, myocardial infarction, or cardiomyopathy were excluded. The remaining 443 autopsy patients were the subjects of our study. The heart weight at autopsy was corrected for body surface area. Genomic DNA was purified from the kidney, and ACE genotype was determined by polymerase chain reaction. Heart weight in the DD genotype (249.9±49.9 g/m 2 ) was significantly higher than that in the ID (230.0±51.2 g/m 2 ; P 2 ; P r =0.145, P r =0.147, P =0.0019). Multiple regression analysis showed that a history of hypertension ( P P =0.0001), and DD genotype ( P =0.0154) were independent predictors of heart weight. Conclusions —ACE genotype predicts cardiac mass; however, it was less effective than epigenetic factors such as hypertension or age.