Serum high molecular weight (HMW) adiponectin improves insulin sensitivity, and a decreased level of serum HMW adiponectin has been reported as a risk factor for the development of diabetes and coronary heart disease. This association may be further confounded by the hemoglobin status, which is involved in the development of atherosclerosis. A cross-sectional study was carried out in 2002. Study participants, consisting of 897 men aged 61±14 (mean±standard deviation) years and 1,148 women aged 63±12 years, were randomly recruited from a single community at the time of their annual health examination. Serum HMW adiponectin levels were lowered dose-dependently with an increased hemoglobin level. Stepwise multiple linear regression analyses for serum HMW adiponectin revealed that the hemoglobin status was independently and significantly associated with serum HMW adiponectin levels as well as sex, age, body mass index (BMI), alcohol consumption, total cholesterol, triglycerides, high density lipoprotein cholesterol, antilipidemic medication, uric acid, serum gamma glutamyltransferase, and insulin resistance. Inclusion of hemoglobin levels in the model further increased the coefficient of determination. In stratified analysis, mean serum HMW adiponectin levels were significantly and similarly decreased as hemoglobin levels increased in men, ages ≥ 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance, and there were significant interactions between the two groups for BMI, alcohol consumption and insulin resistance. Hemoglobin status is inversely associated with serum HMW adiponectin levels in community-dwelling persons, especially those aged ≥ 65 years, BMI < 23.0 kg/m(2), alcohol drinkers, and lower insulin resistance groups.