The aim of this study was to compare the use of several biomarkers to identify obese children and adolescents with increased metabolic risk. One hundred sixty-two Caucasian obese children and adolescents (41% males, 9-18 years old) referred to the Istituto Auxologico Italiano between 2003 and 2004 underwent an oral glucose tolerance test. Circulating levels of adiponectin (AD), plasminogen activator inhibitor 1 (PAI-1), interleukin 18 (IL-18), C-reactive protein (CRP), fibrinogen, uric acid, lipids and insulin were measured. Twenty five percent of obese children had the MS defined using World Health Organization-derived child specific criteria. MS subjects had significantly lower AD (p<0.01) and higher log-PAI-1 (p<0.001), uric acid (p<0.0001), and IL-18 (p<0.001). Subjects with AD levels </=median value had a significantly increased risk of having the MS (p<0.0001), as did subjects with uric acid and PAI-1 levels greater than the median. There was no increased risk with elevated IL-18, CRP, or fibrinogen. Hypoadiponectinemia was independently associated with the MS risk (p<0.0001). In conclusion in obese children and adolescents AD is the best predictor of MS and thus of higher cardiovascular disease risk.