In the present study, the effects of both the microstructure and voids on the high-cycle fatigue behaviour of the 316L austenitic stainless steel are investigated by using finite element simulations of polycrystalline aggregates. The numerical analysis relies on a metallurgical and mechanical characterization. In particular, fatigue tests are carried out to estimate the fatigue limits at 2.106 cycles under uniaxial and multiaxial loading conditions (combined tension and torsion and biaxial tension) using both smooth specimens and specimens containing an artificial hemispherical defect. The simulations are carried out with several configurations of crystalline orientations in order to take into account the variability of the microstructure in the predictions of the macroscopic fatigue limits. These predictions are obtained, thanks to a probabilistic fatigue criterion using the finite element results. The capability of this criterion to predict the influence of voids on the average and the scatter of macroscopic fatigue limits is evaluated.