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Background: Recent studies suggest the role of liver enzymes, such as serum gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) as the predictor for future development of metabolic syndrome (MetS), diabetes and cardiovascular disease in epidemiologic studies. We hypothesized that serum concentrations of GGT and ALT are associated with the development of MetS, according to newly recommended criteria from International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition in Koreans., Methods: A total of 15,250 males (mean 38 y) and 6280 females (mean 41 y) who visited the Health Promotion Center at Kangbuk Samsung Hospital for medical check-up in 2002, were followed-up after 4 y. We analyzed the development of MetS in their follow-up data in 2006., Results: When the subjects were divided into quartiles by the baseline GGT levels, the odds ratio for the MetS defined by both criteria across the quartile groups increased as the quartile groups increased in both gender groups. This association remained significant even after adjustment for confounding factors, such as, age, alcohol intake, smoking status, physical activity, ALT, fasting insulin and HOMA-IR. Serum ALT concentration also showed significantly positive correlation with development of MetS defined by the two criteria even after adjustment for age and GGT in both gender groups. In addition, risk for the individual MetS components increased as the baseline GGT concentrations increased, except low high-density lipoprotein cholesterol (HDL-C) in female group. In receiver operating characteristic (ROC) curves, the area under the curves (AUC) of GGT and ALT to predict future MetS by both criteria was larger than the AUCs of blood pressure, fasting glucose and HDL-C., Conclusions: In this large prospective study in Koreans, high baseline GGT and ALT concentrations predicted future development of MetS defined by IDF and AHA/NHLBI criteria after 4 y of follow-up.