Adiponectin is an adipocyte-specific secretory protein that is highly and specifically expressed in adipose tissue, and low plasma levels of adiponectin are associated with coronary artery disease (CAD). It has been suggested that high molecular weight (HMW) adiponectin is more important for vascular protection than total amount of adiponectin. To establish the clinical relevance of HMW adiponectin, we measured its serum levels in 149 patients with CAD. The levels were lower in vasospastic angina pectoris (3.4 +/- 2.4 microg/ml, p <0.01), stable angina pectoris (3.3 +/- 2.6 microg/ml, p <0.001), and healed myocardial infarction (3.8 +/- 2.9 microg/ml, p <0.01) than chest pain syndrome (controls) (6.6 +/- 5.4 microg/ml). The levels were also lower in multivessel CAD (3.4 +/- 2.4 microg/dl) compared with single vessel CAD (4.2 +/- 2.7 microg/ml, p <0.05) or no organic stenosis (5.1 +/- 3.5 microg/ml, p <0.01). In univariate analysis, diabetes mellitus (p = 0.03), insulin resistance (p = 0.06), high-sensitivity C-reactive protein levels (p = 0.0012), and low HMW adiponectin levels (p = 0.0001) predicted cardiovascular events during 7 years of follow-up. However, multivariate analysis showed that only HMW adiponectin levels were an independent predictor of cardiovascular events (relative risk 2.79, 95% confidence interval 1.49 to 5.24, p = 0.0014). In conclusion, serum HMW adiponectin levels may serve as a predictor of future cardiovascular events in patients with CAD as well as a marker for severity of CAD.