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Summary. Background: Previous studies have reported conflicting results on the relation between serum osteoprotegerin (OPG) concentration and carotid intima media thickness (CIMT). Patients/methods: The present study was conducted to investigate the relations between OPG, risk factors for cardiovascular diseases (CVD) and carotid intima media thickness (CIMT) in a large cross-sectional study including 6516 subjects aged 25–85 years who participated in a population-based health survey. Results: CIMT increased significantly across tertiles of OPG after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index (BMI), systolic blood pressure, CVD and diabetes mellitus (P < 0.0001). There was a significant interaction between age and OPG (P = 0.026). The risk of being in the uppermost quartile of CIMT was reduced (OR 0.52, 95% CI 0.30–0.88) with each standard deviation (SD) higher level of OPG in subjects < 45 years (n = 444), whereas subjects ≥ 55 years of age (n = 4884) had an increased risk of being in the uppermost quartile of CIMT (OR 1.19, 95% CI 1.10–1.29) after adjustment for traditional CVD risk factors. Conclusions: Age has a differential impact on the association between OPG and CIMT in a general population. The present findings may suggest that increased serum OPG does not promote early atherosclerosis in younger subjects.