Purpose: Revolutionary endovascular treatments are on the verge of being available for management of ascending aortic diseases. Morphometric measurements of the ascending aorta have already been done with ECG-gated MDCT to help such therapeutic development. However the reliability of these measurements remains unknown. The objective of this work was to compare the intraobserver and interobserver variability of CAD (computer aided diagnosis) versus manual measurements in the ascending aorta. Methods and materials: Twenty-six consecutive patients referred for ECG-gated CT thoracic angiography (64-row CT scanner) were evaluated. Measurements of the maximum and minimum ascending aorta diameters at mid-distance between the brachiocephalic artery and the aortic valve were obtained automatically with a commercially available CAD and manually by two observers separately. Both observers repeated the measurements during a different session at least one month after the first measurements. Intraclass coefficients as well the Bland and Altman method were used for comparison between measurements. Two-paired t-test was used to determine the significance of intraobserver and interobserver differences (alpha = 0.05). Results: There is a significant difference between CAD and manual measurements in the maximum diameter (p = 0.004) for the first observer, whereas the difference was significant for minimum diameter between the second observer and the CAD (p <0.001). Interobserver variability showed a weak agreement when measurements were done manually. Intraobserver variability was lower with the CAD compared to the manual measurements (limits of variability: from -0.7 to 0.9 mm for the former and from -1.2 to 1.3 mm for the latter). Conclusion: In order to improve reproductibility of measurements whenever needed, pre- and post-therapeutic management of the ascending aorta may benefit from follow-up done by a unique observer with the help of CAD.