<p>Aortic dissection (AD) caused by the intimal tear would progress into the separation of aortic media, leading to devastating sequelae. Quantifying the mechanical and histological changes in aortic intima-media (IM) tissue during the AD development would advance our understanding of the mechanism behind the disease initiation for its prevention and management. Twenty-eight ascending aortic specimens were harvested from 19 patients with type A AD and 9 organ donors to obtain 120 aortic IM tissue samples. Uniaxial tensile experiments were performed on the samples until they failed, and their ultimate stress and stretch data at the time of failure were recorded. Additionally, an extra subsample was cut from each aortic specimen to perform the histological staining to quantify the contents of elastic and collagen fibers. Our statistical results showed that the ultimate stress and stretch of the dissected aortic IM samples were significantly lower than those of normal ones. Furthermore, a positive correlation between the elastic fiber content and ultimate stretch in aortic IM was found. Combining these findings, it suggests that reduced elastic fiber content in aortic IM tissue of the diseased group impairs its ability to withstand high stress and stretch conditions, thereby predisposing to AD.</p> Graphical Abstract <p></p>