Thyroid hormones play an important role in regulating energy homeostasis and lipid and glucose metabolism. This study assessed the relationship between free thyroxine and clinical features of metabolic syndrome (MS). A total of 4,938 Taiwanese subjects (2,891 men and 2,047 women with a mean age of 50.1+/-12.6 years) with normal serum free thyroxine levels were enrolled. A modified National Cholesterol Education Program definition of MS was adopted substituting body mass index (BMI) for waist circumference. Serum free thyroxine concentrations were determined by immunoassay. Overall, 14% of subjects had a high fasting glucose, 27% had high blood pressure, 14% had high serum total triglyceride, 8% had low high-density lipoprotein cholesterol, and 18% were obese. The serum free thyroxine concentrations showed a statistically significant correlation with triglyceride and body mass index, respectively (P<.01), but not with blood pressure, glucose level, or high-density lipoprotein cholesterol level. According to the presence of 0, 1, 2, and 3 or more features of MS, age and sex-adjusted means of serum free thyroxine were 17.8+/-3.7, 17.6+/-3.7, 17.5+/-3.7, and 17.1+/-3.3 pmol/L, respectively, with a modest, but statistically significant, decreasing trend (P<.05). When comparing subjects in the highest and lowest quartile of free thyroxine, the former group demonstrated a 2-fold decrease in the odds ratio for MS with 3 or more metabolic features. Low circulating free thyroxine levels, albeit normal, were associated with MS in a Chinese population. Further study is necessary to document the role of thyroid hormones in metabolic abnormalities of MS.