Background: Few studies have examined the effect of insulin resistance on the association between alanine aminotransferase (ALT) and metabolic syndrome. The association between ALT levels and metabolic syndrome were determined, independently of insulin resistance in Korean populations. Methods and Results: The association between ALT and metabolic syndrome were examined in 28,456 subjects who visited 7 Health Promotion Centers at University Hospitals in Korea from 2006 to 2008. HOMA-IR index was used to represent insulin resistance index. ALT levels were found to be positively associated with metabolic syndrome after adjusting for age, alcohol intake, and smoking status. Furthermore, when additional adjustment was made for insulin resistance, this association between ALT and metabolic syndrome, although slightly attenuated, remained strongly significant. Subjects in the highest ALT quartile were found to have a higher risk of having metabolic syndrome than those in the lowest quartile (odds ratio (OR)=4.45, 95% confidence interval (CI)=3.96-4.99 for men and OR=3.51, 95%CI=2.73-4.52 for women). In addition, the association between ALT level and the risk of metabolic syndrome was significantly higher in the relatively low risk group. Conclusions: ALT levels were found to be significantly associated with metabolic syndrome independently of insulin resistance and with an interaction by age. Further cohort studies are needed to determine the usefulness of ALT levels for predicting the risk of metabolic syndrome. (Circ J 2011; 75: 964-969)