Fatigue resistance of Nitinol stents implanted into femoro-popliteal arteries is a critical issue for the particular biomechanical environment of this district. Hip and knee joint movements due to the cyclic daily activity expose the superficial femoral artery (SFA), and therefore the implanted stents, to quite large and cyclic deformations influencing stent fatigue resistance. Objective of this work is to provide a tool based on finite element analysis able to evaluate the biomechanical effect of SFA on stent fatigue resistance. Computer simulations of the treatment of stenotic vessel by angioplasty and stenting and of the subsequent in vivo loading conditions (axial compression and bending) were carried out. Three different stenotic vessel models were defined, by keeping a constant stenosis rate and changing the plaque sharpness and number of stenoses. The fatigue behaviour was analysed comparing the amplitude and mean value distribution of the first principal strain in the whole stent for the different simulated conditions. Results showed that the maximum mean strain is similar in all the models, while the alternating strain is related to both plaque shape and loading conditions. In conclusion, this study confirms the requisite of replicating in vivo loading conditions. It also reveals the importance of taking into account the thickness variation of the vessel in the stenotic zone in the assessment of the stent fatigue resistance.