Background <p>The triple rule-out computed tomography angiography (TRO-CTA) has recently emerged as a technique that noninvasively evaluates the coronary arteries (CAs), the pulmonary arteries (PAs) and the thoracic aorta (TA).</p> Objective <p>To evaluate the feasibility of an optimized scanning protocol to reduce the volume of iodine contrast media (ICM), injection rate, and radiation dose in patients undergoing TRO-CTA.</p> Methods <p>Patients undergoing TRO-CTA were assigned to either group A or group B using a 16&#xa0;cm wide-detector CT. Patients in group A were imaged with a traditional triple scanning protocol with a sequence of the PA, CAs, and TA. Patients in group B were imaged using the modified protocol with scanning sequence of PA, TA, and CAs, ICM of 55&#xa0;ml, and injection rate of 4.5 mL/s. The image quality and effective radiation dose (ED) were compared.</p> Results <p>There were no significant differences in basic information between groups A and B. Other than the left PA, RA, and RV, there were no significant differences in the CT attenuation values of relevant vascular structures between groups A and B. There were no significant differences in CNR values between the two groups except the LAD-D and LCX. The image quality scores were comparable between groups A and B except the CAs. However, there were significant differences between the two groups in ICM (<i>p</i> &lt; 0.05), scanning time (<i>p</i> &lt; 0.001) and ED (<i>p</i> = 0. 023).</p> Conclusions <p>The optimized TRO-CTA scanning protocol can achieve less ICM and lower ED while maintaining image quality.</p>