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Introduction: Patient-specific computational models are a powerful tool for planning cardiovascular interventions. However, the in vivo patient-specific mechanical properties of vessels represent a major source of uncertainty. In this study, we investigated the effect of uncertainty in the elastic module (E) on a Fluid–Structure Interaction (FSI) model of a patient-specific aorta. Methods: The image-based χ-method was used to compute the initial E value of the vascular wall. The uncertainty quantification was carried out using the generalized Polynomial Chaos (gPC) expansion technique. The stochastic analysis was based on four deterministic simulations considering four quadrature points. A deviation of about ±20% on the estimation of the E value was assumed. Results: The influence of the uncertain E parameter was evaluated along the cardiac cycle on area and flow variations extracted from five cross-sections of the aortic FSI model. Results of stochastic analysis showed the impact of E in the ascending aorta while an insignificant effect was observed in the descending tract. Conclusions: This study demonstrated the importance of the image-based methodology for inferring E, highlighting the feasibility of retrieving useful additional data and enhancing the reliability of in silico models in clinical practice.