Electro-mechanical actuators including planetary roller screw (PRS) support cyclic loads in aeronautical conditions. PRS multiple thread contacts between screw, rollers and nut allow the mechanism to support large loads. However, aeronautical accreditation requires fine prediction of fatigue lifespan. In this paper, a fatigue design strategy for PRS mechanisms is proposed combining Hertz contact model and a multi-axial fatigue criterion. The method is applied on two examples, one standard and one inverted PRS. The lifespan of PRS mechanism depends on maximal Dang Van stress. The Hertz sliding angle (Hertz contact main direction/sliding velocity) was introduced to analyze PRS performances. For both examples, the maximum stress at thread contact were located in bulk material but not at the surface. Dang Van stress mainly depended on curvature ratio, Hertz sliding angle and loads. Based on this analysis, Dang Van criterion was implemented to derive the loading domain of infinite lifespan of the mechanism. Critical contact was not always on the roller-screw side.