Objective To determine the relationship between estimated calcaneal bone mineral density (BMD) and arterial stiffness in hemodialysis patients. Methods Forty one patients on maintenance hemodialysis were recruited. Estimated calcaneal BMD was measured by a calcaneal quantitative ultrasound instrument. Stiffness index β of the right common carotid artery (CCA) was measured using an ultrasonic phase-locked echo-tracking system (Prosound a10; Aloka, Japan) equipped with a high-resolution real-time 7.5-13 MHz linear scanner. Stiffness index β = [ln (Ps/Pd)]/[(Ds-Dd)/Dd], where Ps and Pd are the brachial systolic and diastolic blood pressures, respectively, and Ds and Dd are the systolic and diastolic inner diameters of CCA, respectively. Serum 25-hydroxyvitamin D3 and intact parathyroid hormone (iPTH) were detected by electrochemiluminescence. Serum calcium, phosphorus, C-reactive protein, albumin, total cholesterol, high density lipoprotein, low density lipoprotein and triglyceride were determined with standard methods. Results The mean age of the patients was 57.0±12.3 years. The mean estimated calcaneal BMD was -2.1±0.8, meaning that 14.6% of the patients had osteoporosis, and 58.5% had osteopenia. Pearson correlation analysis indicated that stiffness index β was negatively correlated with calcaneal BMD (r=-0.453, P=0.002) and 25-hydroxyvitamin D3 (r=-0.337, P=0.031), and was positively correlated with serum phosphorus (r=0.391, P=0.022), mean arterial pressure (r=0.298,P=0.043) and age (r=0.477, P=0.002), but had no correlation with serum calcium, iPTH, C-reactive protein, albumin, and lipids. Multiple stepwise regression analysis showed that age (β=0.311, P=0.008) and calcaneal BMD (β=-0.218,P=0.043) were the independent variables responsible for stiffness index β. Estimated calcaneal BMD was positively correlated with 25-hydroxyvitamin D3 (r=0.315, P=0.049) and negatively correlated with age (r=-0.381, P=0.014) and serum phosphorus (r=-0.323, P=0.046), but had no correlation with serum calcium and iPTH. Conclusion Calcaneal osteopenia is prevalent in hemodialysis patients, and it is independently correlated with carotid arterial stiffness.