To evaluate whether the patient-specific contrast enhancement optimizer simulation software (p-COP) is useful for predicting contrast enhancement during whole-body computed tomography angiography (WBCTA). We randomly divided the patients into two groups using a random number table. We used the contrast material (CM) injection protocol selected by p-COP in group A (n = 52). The p-COP used an algorithm including data on the individual patient’s cardiac output. Group B (n = 50) was assigned to the conventional CM injection protocol based on body weight. We compared the CT number in the abdominal aorta at the celiac artery level between the two groups and classified them as acceptable (> 280 HU) and unacceptable (< 279 HU) based on the optimal CT number for the WBCTA scans. To evaluate the difference in both injection protocols, we compared the visual inspection of the images of the artery of Adamkiewicz in both protocols. The CM dosage and injection rate in group A were significantly lower than those in group B (480.8 vs. 501.1 mg I/kg and 3.1 vs. 3.3 ml/s, p < 0.05). The CT number of the abdominal aorta at the celiac level was 382.4 ± 62.3 HU in group A and 363.8 ± 71.3 HU in group B (p = 0.23). CM dosage and injection rate were positively correlated to cardiac output for group A (r = 0.80, p < 0.05) and group B (r = 0.16, p < 0.05). The number of patients with an acceptable CT number was higher in group A [46/6 (86.7%)] than in group B [43/7 (71.4%)], but not significant (p = 0.71). The visualization rate for the Adamkiewicz artery was not significantly different between groups A and B (p = 0.89). The p-COP was useful for predicting contrast enhancement during WBCTA with a lower CM dosage and a lower contrast injection rate than that based on the body weight protocol. In patients with lower cardiac output a reduction in contrast injection rate and CM dosage did not lead to a reduced imaging quality, thus particularly in this group CM dosage can be reduced by p-COP.