In plasma, adiponectin is the most abundant adipocyte-specific protein. Low levels of adiponectin have been shown to be associated with obesity, type 2 diabetes, dyslipidemia and coronary artery disease (CAD), but the underlying mechanisms are incompletely understood. We speculated that the influence of adiponectin on the lipid profile and CAD risk could, in part, be mediated by lipoprotein lipase (LPL), because like adiponectin, LPL is secreted from adipose tissue, and low LPL is related to dyslipidemia and CAD. To test this hypothesis, we quantitated adiponectin levels in plasma by ELISA and used an artificial emulsion and an ELISA to measure LPL activity and concentration in the post heparin plasma of 245 patients undergoing elective coronary angiography. In our patients, low adiponectin was associated with low HDL cholesterol (p<0.001), elevated plasma triglycerides (p<0.001) and VLDL cholesterol (p<0.001), and the extent of CAD (number of diseased vessels, p=0.002 and CAD extent score, p=0.003). In multivariate analysis including age, BMI, insulin levels and polymorphisms in the LPL gene, adiponectin was the factor with the greatest influence on LPL activity (p=0.002) and concentration (p<0.01). For quartiles of increasing adiponectin levels, there was a continuous increase of LPL activity (144±57, 170±69, 175±73, 192±64 nmol/ml/min, p=0.003) and concentration (237±90, 291±100, 302±112, 348±153 ng/ml, p<0.001). Additionally, low adiponectin was associated with lower LPL concentration (r=0.353, P<0.001) and LPL activity (r=0.315, P=0.001) in a cohort of 108 type 2 diabetic patients. These data show that in both, patients with CAD and type 2 diabetics, adiponectin is strongly associated with LPL levels in vivo, and that at least part of the effect of adiponectin on lipid profile and CAD risk may be mediated by LPL.