The radial transport across the wall of expanded polytetrafluoroethylene (ePTFE) arterial prostheses has a significant effect on lipid uptake observed in prostheses implanted in humans, which has been postulated to be one of the causes associated with implant failure. The goal of this study was to stimulate radial transport on a lipidic dispersion across the wall of an ePTFE prosthesis and investigate its effects on the circumferential mechanical properties of the prosthesis. An in vitro model was developed to simulate the lipidic radial transport across the wall. Lipids contained in a phosphatidylcholine dispersion were used as the transported molecules. Lipid concentration profiles were obtained after exposing commercial ePTFE prostheses to various transmural pressure and/or lipidic concentration gradients. Phospholipids gradually accumulated up to the external reinforcing wrap of the prosthesis, which clearly acted as a rigid barrier against lipid infiltration. Tensile tests performed on the virgin samples showed that the wrap was much more rigid than the microporous part of the prosthesis. After the lipid simulation, the rigidity of the wrap decreased with respect to what was observed for the virgin prosthesis. Finally, some clinical implications of this phenomena are discussed.