Ascending thoracic aortic aneurysm (aTAA) is a major cause of human deaths. Despite important recent progress to better understand its pathogenesis and development, the role played by deranged hemodynamics on aTAA risk of rupture is still partially unknown. Our aim was to develop and apply a novel methodology to assess the correlation between aTAA rupture risk and hemodynamic biomarkers combining for the first time in vivo, in vitro and in silico analyses. Computational fluid dynamic (CFD) analyses were performed and validated on 10 patients using patient specific data derived from CT scan and 4D MRI. Systolic wall shear stress (WSS), time averaged wall shear stress (TAWSS), flow eccentricity (Flow eccentricity) and helicity intensity (h2) were assessed. A bulge inflation test was carried out in vitro on the 10 aTAA samples resected during surgical repair. The biomechanical and rupture properties of these samples were derived: the burst pressure, the physiological tangent elastic modulus (𝐄𝐩𝐡𝐲𝐬𝐢𝐨), the Cauchy stress at rupture (𝛔𝐫𝐮𝐩𝐭), the rupture stretch (𝛌𝐫𝐮𝐩𝐭) and the rupture stretch criterion (ϒ𝒔𝒕𝒓𝒆𝒕𝒄𝒉). Statistical analysis was performed to determine correlation between all variables. Results: Statistically highly significant (p<0.01) positive correlation between 𝛌𝐫𝐮𝐩𝐭 and the TAWSS (r=0.867 and p=0.001) was found. This project, shows that relatively low TAWSS significantly correlates with reduced rupture properties in aTAAs. Understanding the pathogenesis of aTAA remains crucial to reduce morbidity and mortality. Our aim is to establish possible correlations between aTAA rupture risk and hemodynamic biomarkers by combining for the first time in vivo, in vitro and in silico analyses.