Endovascular treatment of the femoro-popliteal artery has recently become a valuable therapeutic option for popliteal arterial aneurysms. However, its efficacy remains controversial due to the relatively high rate of complications, such as stent occlusion as result of intra-stent thrombosis. The elucidation of the interplay among vessel geometrical features, local hemodynamics, and leg bending seems crucial to understand onset and progression of popliteal intra-stent thrombosis. To this aim, patient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm by stent-grafts and experiencing intra-stent thrombosis. Both Newtonian and non-Newtonian blood rheological models were considered. Results were presented in terms of tortuosity, luminal area exposed to low (< 0.4 Pa) and high (> 1.5 Pa) time-averaged wall shear stress (TAWSS), area exposed to high (> 0.3) oscillatory shear index (OSI), and flow helicity. Study outcomes demonstrated that leg bending induced significant hemodynamic differences (> 50% increase) in both patients for all the considered variables, except for OSI in one of the two considered patients. In both leg configurations, stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity, low velocity, low helicity, low TAWSS, and high OSI; while the distal part has higher tortuosity, velocity, helicity, TAWSS, and lower OSI. Sensitivity study on applied boundary conditions showed that the different inlet velocity profiles for a given inlet waveform affect slightly the numerical solution; conversely, the shape and magnitude of the prescribed inlet waveform is determinant. Focusing on the comparison between the Newtonian and non-Newtonian blood models, the area with low TAWSS is greater in the Newtonian model for both patients, while no significant difference occurs between the surfaces with high TAWSS.GraphicPatient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm and experiencing intra-stent thrombosis. Both Newtonian and non-Newtonian blood rheological models were considered. In both straight and bent leg configurations, stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity, low velocity, low helicity, low time-averaged wall shear stress (TAWSS), and high oscillatory index (OSI); while the distal part has higher tortuosity, velocity, helicity, TAWSS, and lower OSI.