Objective: This study aimed to examine the utility of pyridinoline (Pyd) and deoxypyridinoline (Dpd) cross-links in the detection of subclinical atherosclerosis in postmenopausal women with or without osteoporosis. Methods: We measured Pyd, Dpd, carotid intima-media thickness (CIMT), fasting total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and blood pressure in 59 healthy postmenopausal women: 30 had normal bone mineral density (group I) and the remaining 29 had osteoporosis or osteopenia (group II) according to World Health Organization criteria. Results: There were no statistically significant differences in age, duration of menopause, age at menopause, lipid profile, body mass index, Pyd level, Dpd level, and Pyd-to-Dpd ratio between the groups (P > 0.05). No significant difference in CIMT was found when groups I and II were compared (P = 0.538). No statistically significant differences in Pyd level, Dpd level, and Pyd-to-Dpd ratio were found when women with CIMT higher than 5 mm and women with CIMT of 5 mm or less were compared in groups I and II (P > 0.05). However, significantly declined Dpd level and increased Pyd-to-Dpd ratio were found in women with CIMT higher than 5 mm when compared with women with CIMT of 5 mm or less. CIMT was found to be negatively correlated with Dpd level (r = -0.346, P = 0.007) and to be positively correlated with the Pyd-to-Dpd ratio (r = 0.702, P < 0.001). Conclusions: The increase in the Pyd-to-Dpd ratio, irrespective of the participants' bone mineral density, may have predictive value in the determination of subclinical atherosclerosis in postmenopausal women.