Growing evidence suggests that hypoadiponectinemia may play a significant role in the development of the metabolic syndrome (MetS). The relationships of serum adiponectin with MetS itself and components of MetS were investigated in a non-diabetic general population. We performed a cohort study conducted on a Korean senior (age > 40 years) population with 2,471 men and 3,463 women without history of cardiovascular disease, diabetes or cancer. MetS was defined according to the Asian modified criteria of the Adult Treatment Panel III report. Serum adiponectin concentrations were measured by radioimmunoassay. The median adiponectin level in Mets was also significantly lower than that in non-Mets patients in men (6.00 vs. 8.00 µg/mL, p <0.001) and women (10.12 vs. 11.74 µg/mL, p <0.001). The median serum adiponectin levels in male with 0, 1, 2, 3, or ��� 4 components of MetS were 8.90, 8.11, 7.31, 6.05, and 5.74 µg/L, respectively (p trend <0.001), while those in women were 12.82, 11.99, 11.38, 10.65, and 9.38 µg/L, respectively (p trend <0.001). Adiponectin concentration was correlated negatively with waist circumference, triglyceride, hsCRP, fasting glucose, and insulin, and correlated positively with high-density lipoprotein and age in both sexes (p <0.001). In a multivariate regression model, after adjustment for age, body mass index, smoking, CRP and lipid profiles, the odds ratio of MetS, comparing extreme quartiles of adiponectin distribution, was 0.32 (95% confidence interval [CI], 0.20 to 0.50) in men and 0.57 (95% CI, 0.43 to 0.76) in women. In conclusion, adiponectin level is strongly associated the phenotype of MetS, as well as components of MetS in the non-diabetic general population.