OBJECTIVE - Increased adiponectin levels may play a protective role in the development of metabolic abnormalities, but prospective studies of the predictive value of serum adiponectin to identify individuals at high risk of new-onset metabolic syndrome are lacking. We investigated whether serum adiponectin predicts incident cases of the metabolic syndrome in a populationbased longitudinal study. RESEARCH DESIGN ANDMETHODS - A prospective cohort study was conducted of 2,044 adults (831 men and 1,213 women) aged 40-70 years without metabolic syndrome examined in 2005-2008 (baseline) and 2008 - 2011 (follow-up). Baseline serum adiponectin concentrations were measured by radioimmunoassay. RESULTS - During an average of 2.6 years of follow-up, 153 men (18.4%) and 199 women (16.4%) developed metabolic syndrome. In multivariable-adjusted models, the odds ratio for incident metabolic syndrome comparing the highest with the lowest quartiles of adiponectin levels was 0.25 (95% CI 0.14-0.47) in men and 0.45 (0.28-0.74) in women. While serum adiponectin did not improve the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components, the net reclassification improvement and the integrated discrimination improvement of prediction models including adiponectin were significantly higher compared with those of models not including adiponectin among men, with a signi ficant difference between men and women (P = 0.001). CONCLUSIONS - Increased adiponectin is an independent protective factor for incident metabolic syndrome in men and women, and it may have a clinical role in predicting new-onset metabolic syndrome among men.