Few studies have examined an association between SNP276 and the risk of metabolic syndrome (MetS), which accelerates the development of diabetic complications, in patients with type II diabetes mellitus (T2DM). This study examined whether the SNP276G4T polymorphism is associated with risk of MetS in 673 Korean patients with T2DM from an ongoing prospective study. Multiple logistic regression analysis revealed that the OR for MetS was greater in patients with the TT genotype than in those with the GG genotype (OR ¼ 2.071; 95% CI ¼ 1.088-3.943) after adjustment of the putative risk factors for MetS. After examining the relationship between serum adiponectin and MetS risk for each genotype, only in patients with the GT genotype, serum adiponectin was negatively associated with the risk of MetS (OR ¼ 0.287; 95% CI ¼ 0.193-0.427). The SNP276G4T polymorphism may have an independent role in the determination of MetS in Korean patients with T2DM.