Osteoprotegerin (OPG) appears to represent the molecular link between bone resorption and vascular calcification, and may help to explain the high prevalence of atherosclerosis and osteoporosis in postmenopausal women. We investigated a possible association between serum OPG levels and arterial stiffness in postmenopausal women with osteoporosis. 70 postmenopausal women with osteoporosis and cardiovascular risk factors but without coronary artery disease were evaluated for metabolic, inflammatory parameters and serum OPG levels. Pulse wave velocity (PWV) and augmentation index (AIx) were performed as a simple noninvasive recording of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). Serum OPG levels were significantly, positively associated with AIx (r=0.39, p=0.003) and with PWV (r=0.81, p<0.0001). No association between OPG levels and hemodynamic variables or measures of glucose metabolism was observed. Among inflammatory markers, OPG was significantly, positively associated with fibrinogen (r=0.323, p=0.015). In a multiple linear regression analysis, OPG was independent predictor of PWV (standardized beta=0.75, p<0.0001) and AIx (standardized beta=0.41, p=0.01). Serum OPG is potentially an independent predictor of early vascular adverse changes in osteoporotic postmenopausal women.