Osteoprotegerin (OPG) plays a core role in bone reformation by antagonizing the effect of receptor activator of nuclear factor kappa-B ligand (RANKL), and mediates vascular calcification in cardiovascular disease patients. Thus, we aimed to examine the relationship between serum OPG levels and cardiovascular factors and inflammatory markers in metabolic syndrome patients (MS). This cross-sectional study included 96 men who visited the diet clinic between May and July 2011. Patients were classified into 2 groups based on NCEP-ATP guidelines: normal and with MS (n = 50 and 46, respectively). Physical measurements, biochemical assay were measured. Serum OPG and IL-6, diponectin and hs-CRP were assessed. MS were aged 50.02 +/- 10.85 years, and normal patients 52.07 +/- 9.56 years, with no significant differences. Significant differences were not observed in BMI between the 2 groups. Moreover, significant differences were not observed in serum OPG, however, the serum OPG level (4.41 +/- 1.86 pmol/L) differed significantly between an overweight MS (BMI > 25) and normal patients. OPG was correlated to age (r = 0.410, p = 0.000), HDL-cholesterol (r = 0.209, p = 0.015), and log adiponectin (r = 0.175, p = 0.042). Multiple regression analyses using the enter method showed that age (beta = 0.412, p = 0.000) and BMI (beta = 0.265, p = 0.000) considerably affected OPG. In conclusion, out study showed that serum OPG levels are correlated with cardiovascular risk factors, such as BMI, HDL-cholesterol and adiponectin in MS and adiponectin, suggesting that serum OPG has potential as a cardiovascular disease indicator and predictor.