Nickel-Titanium alloys (Nitinol) are widely used for biomedical applications. Peripheral stents are almost exclusively composed of Nitinol, as its superelasticity is suited for minimally-invasive insertion and durable effect. After crimping and deployment stents undergo cyclic multi-axial loads imposed by vascular and lower-limb motion (e.g. axial compression, bending, and torsion). This complex mechanical environment could lead to metal fatigue and device fracture, with possible severe consequences (e.g. in-stent restenosis). Standard regulations require experimental verification of stent fatigue behaviour for preclinical assessment, but no exact indications are provided to direct the load combination. Moreover, different fatigue criteria were developed for common metals to predict fatigue endurance, but no criteria were specifically defined for the unique thermo-mechanical properties of Nitinol. This study investigated the role of cyclic multi-axial loading conditions on different stent geometries, looking at how they affect the stress/strain distribution along the device and how different criteria may affect the fatigue prediction (e.g. the standard Von Mises alternate approach and other critical plane approaches). Then, a preliminary experimental fatigue campaign was performed in agreement with the numerical simulations in order to compare the numerical predictions with the experimental results. The result suggest that the critical plane approaches are more reliable than the standard Von Mises criterion.