Abstract: This study investigates the fatigue behavior of railway rails with lubrication holes through a finite element modeling approach validated against full-scale laboratory tests. Fatigue tests were conducted on rail coupons subjected to three-point bending with the rail positioned upside-down, replicating the most critical loading configuration. Two finite element models were developed using ANSYS 2024 R2: a reduced model reproducing the laboratory setup, and a more comprehensive model representing a real rail track segment with multiple spans. The first model was calibrated against experimental S-N curve data to ensure consistency with the mechanical behavior observed in tests. The second model was used to evaluate the effect of wheel position, hole diameter, and hole location on the fatigue life of the rail. Simulation results highlight the influence of geometric and load parameters on crack initiation near the hole, providing valuable insights for optimizing hole design and placement in operational conditions.