The present paper introduces a methodology for the high-cycle fatigue design of balloon-expandable stents. The proposed approach is based on a micromechanical model coupled with a probabilistic methodology for the failure prediction of stents. This allows to account for material heterogeneity and scatter, to introduce a fatigue criterion able to consider stress gradients, and to perform a probabilistic analysis to obtain general predictions from a limited number of realizations of microstructures investigated. Numerical simulations have allowed to highlight the noteworthy characteristics of the mechanical response in the stent as well as the heterogeneity of the mechanical fields due to stress concentrations in the unit cell geometry and to strain incompatibilities between the grains induced by the anisotropy of their mechanical behavior. The predicted survival probability of the stent is in accordance with the experimental data from the literature. Moreover, the influence of the amplitude of the arterial pressure on the fatigue strength of the stent has been evaluated.