Adiponectin is an adipocyte-specific secretory protein, which possesses antidiabetic and antiatherosclerotic properties. Adiponectin exists as multimers in serum, and high-molecular-weight (HMW) adiponectin is particularly considered to be the active form of the protein. The objective of the present study was to examine whether decreased HMW adiponectin is a predictor of progression to metabolic syndrome during a 6-year follow-up period in Japanese men. The study subjects were 416 Japanese men without metabolic syndrome, aged 30 to 59 years at baseline, who had participated in annual health checkups in both 2000 and 2006. Low concentration of HMW adiponectin (< or =2.65 microg/mL) was associated with substantially higher hazard ratio of the progression to metabolic syndrome after adjustment for age and body mass index (hazard ratio, 1.561; 95% confidence interval, 1.051-2.292; P = .028). The number of subjects with the progression to metabolic syndrome in each tertile based on baseline HMW adiponectin concentration was significantly different among the 3 groups (HMW adiponectin: chi(2) = 7.473, P = .0238; total adiponectin: chi(2) = 4.477, P = .1066; HMW-total adiponectin ratio: chi(2) = 1.676, P = .4325). It was suggested that decreased HMW adiponectin is a predictor of the progression to metabolic syndrome in a 6-year follow-up study of Japanese men. Furthermore, it was suggested longitudinally that measuring HMW adiponectin is efficient to predict the progression to metabolic syndrome compared with measuring total adiponectin or HMW-total adiponectin ratio.