The objective of our study was to assess the potential of 64-slice computed tomography angiography (64-CTA) for whole-body evaluation of atherosclerosis burden. Seventy-eight patients referred for coronary imaging underwent whole-body 64-CTA using an adjusted strategy for the administration of contrast medium with dose-saving algorithms involving ECG modulation and reduced tube voltage. Arterial segments (15 coronary, 32 systemic) were evaluated for significant (≥50%) steno-occlusive disease while arterovenous density was evaluated at seven extracoronary locations. Homogeneous attenuation (mean 321±20 HU) was obtained throughout the systemic vasculature. Atherosclerosis was observed in 238/995 (24%) coronary and 368/2441 (15%) systemic segments. Significant stenoses/occlusions were present in 214 (21%)/24 (2.5%) coronary segments while asymptomatic clinically relevant stenoses were present in 49 systemic segments. Sensitivity, specificity, positive and negative predictive values of coronary 64-CTA among 52 patients who also underwent quantitative coronary angiography were 92%, 95%, 81% and 98%, respectively.