A recent study has demonstrated that adiponectin inhibited hypertrophic signaling in the myocardium of mice, implying that a decrease in the blood adiponectin level could cause cardiac muscle hypertrophy. We hypothesized that a relationship might exist between the serum adiponectin level and electrocardiographically diagnosed left ventricular hypertrophy (ECG-LVH), and we examined this hypothesis by epidemiological study of 2839 Japanese male workers who were not taking medications for hypertension. ECG-LVH was defined as meeting Sokolow-Lyon voltage criteria and/or Cornell voltage-duration product. The subjects were categorized by tertiles of serum adiponectin level, and a multivariate logistic regression analysis was conducted relating left ventricular hypertrophy to adiponectin tertiles adjusting for potential confounding factors. Prevalence of ECG-LVH in the studied sample was 16.7%. Adiponectin ranged from 1.0 to 5.0 microg/mL in the lowest category and from 7.4 to 30.6 microg/mL in the highest. Compared with subjects in the highest adiponectin category, those in the lowest one had a significantly higher prevalence of ECG-LVH independent of age, body mass index, and systolic blood pressure with an odds ratio of 1.50 and a 95% CI of 1.16 to 1.94. Further adjustment for high-density lipoprotein cholesterol, triglyceride, and insulin resistance did not change the association (odds ratio: 1.68; 95% CI: 1.28 to 2.21; P<0.001). Similar results were obtained when different criteria for ECG-LVH were used or when subjects were stratified by blood pressure or body mass index. Adiponectin concentration was inversely and independently associated with ECG-LVH in Japanese men.