Adiponectin exerts anti-inflammatory and antiatherogenic effects and appears to protect against arteriosclerosis. Accordingly, an association between low concentrations of plasma adiponectin and cardiovascular (CV) disease has been demonstrated in several studies. In contrast, elevated plasma adiponectin has been associated with increased mortality and an increasing number of major adverse CV events (MACE). Because of these conflicting results, the true role of adiponectin remains to be elucidated. In the Copenhagen City Heart Study, we prospectively followed up 5,624 randomly selected men and women from the community without CV disease. Plasma adiponectin was measured at the beginning of the study. The median follow-up time was 7.8 years (interquartile range 7.3 to 8.3). The end point was all-cause mortality (n = 801), and the combined end point was MACE, consisting of CV mortality or nonfatal myocardial infarction or ischemic stroke (n = 502). High adiponectin was inversely associated with an increasing number of traditional CV risk factors (p