BACKGROUND: Metabolic syndrome is a cluster of several metabolic disorders (central obesity, dyslipidemia, hyperglycemia, and hypertension). It is closely related to the cardiovascular risk factors. ENPP1 is an inhibitor of insulin-induced activation of the insulin receptor. The aim of this study was to investigate the association between ENPP1 K121Q polymorphism and metabolic syndrome in Korean. METHODS: We measured BMI, waist circumference, blood pressure, lipid profile, fasting glucose in the participants who visited Health Promotion Center, Jeju National University Hospital from February to July 2008. ENPP1 K121Q polymorphism was determined by restriction fragment-length polymorphism polymerase chain reaction in 84 patients with metabolic syndrome and 114 control group. RESULTS: The frequencies of ENPP1 K121Q polymorphism were 27.4% in metabolic syndrome and 9.6% in control group. BMI, waist circumference, blood pressure were increased in male K121Q group and triglyceride was increased in female K121Q group. CONCLUSION: K121Q polymorphism was more frequent in the patients with metabolic syndrome among Koreans. There were differences of the metabolic components according to the genotype. It supports the K121Q polymorphism was associated with the genetic susceptibility for metabolic syndrome.