Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and were compared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD group compared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.