BACKGROUND AND OBJECTIVES: Osteoprotegerin (OPG) is a decoy receptor for receptor nuclear factor-kB ligand (RANKL). We sought to evaluate the association between the serum OPG level and the target lesion calcium (TLC) in those patients suffering with coronary artery disease (CAD). SUBJECTS AND METHODS: We assayed the serum OPG levels in 65 CAD patients (mean age: 62+/-10 yrs, M : F=46 : 19) with using enzyme immunoassay, and these patient underwent intravascular ultrasound (IVUS) examinations of their target lesions. The degree of TLC was estimated by the maximum arc of calcium and also the calcified plaque surface area that was calculated from the serial cross-section IVUS images. RESULTS: The median serum OPG levels were greater in the subjects with TLC than in the subjects without TLC (1.36 vs 0.95 ng/mL, respectively, p<0.05). Significant correlation was noted between the serum OPG levels and the maximum arc of calcium (r=0.274, p=0.027). The median serum OPG levels were significantly increased more in the subjects who had a maximum arc of calcium ranging from 90 to 180 degrees than in those subjects who had a maximum arc of calcium less than 90 degrees (1.63 vs 1.14 ng/mL, respectively, p<0.05) and the median serum OPG levels were also increased more in the subjects who fell within the second tertile of the calcified plaque surface area than that in those subjects who fell within the first and third tertile (0.96, 1.53, 1.40 ng/mL for the first, second, third tertile, respectively, p<0.05). On the stepwise multivariate logistic regression analysis, the serum OPG level remained a risk factor for TLC after adjustment was made for the other risk factors such as age, diabetes mellitus, HbA1C and a smoking history (p=0.019, odds ratio 5.208 [95% confidence interval: 1.308-20.744]). CONCLUSION: In patients with CAD, an increased serum OPG level is associated with target lesion calcification.