To investigate the adaptation of the contrast injection protocol for lower tube potential at cardiovascular computed tomography (CT) angiography, this study analyzed 83 patients (56 100kV vs. 27 120kV) imaged with a prospectively ECG-triggered axial technique for evaluation of aortic disease on a 256-slice CT scanner from 4/10/12 to 5/23/12. A custom algorithm was used to select tube potential and tube current based on patient size. The same contrast injection protocol (contrast concentration 370 mgI/mL, flow rate = 3.5 mL/s, volume = 90 mL) was applied to both cohorts. A Bae-Heiken-Brink pharmacokinetic model was utilized to simulate attenuation in the aorta for the applied contrast protocol in both cohorts and for 3 reduced volumes in the 100kV cohort (A: 72mL, -20%; B: 60mL, -33%; C: 50mL, -44%). Quantitative analysis revealed that 100kV cohort had significantly higher contrast attenuation and signal-to-noise ratio than the 120kV cohort but similar image noise. Simulation of protocol A and B in the 100kV cohort yielded significantly higher attenuation than that measured from the 120kV cohort (p<0.05); attenuation with protocol C showed no significant difference. Simulation results demonstrated that the amount of contrast material can be reduced by as much as 44% for 100 compared to 120 kV imaging but still yielded similar aortic attenuation. A prospective, randomized study should be conducted to validate the performance of the proposed contrast injection protocol at 100kV.