Laser Powder Bed Fusion (L-PBF) of nickel superalloy Inconel 625 (IN625) is widely adopted for fatigue-critical aerospace and energy applications. The accuracy of finite element method (FEM) fatigue predictions depends critically on the Basquin fatigue constants used, yet most FEM studies apply generic material library values without calibration to the actual process-specific material state. This study presents a systematic FEM-based fatigue assessment of L-PBF IN625 specimens (ASTM E466) under constant amplitude axial loading (20–60 kN, R = 0.1) and quantifies the effect of Basquin constant calibration on fatigue life, damage, and safe load predictions. Stress-life (S-N) analysis was performed in ANSYS Workbench 2021 R2 using SOLID187 tetrahedral elements (148,563 nodes; 35,532 elements). The Basquin fatigue strength coefficient was calibrated from published fatigue failure data for L-PBF IN625 (Poulin et al., ≤0.1% porosity, R = 0.1), yielding σ'f = 2050 MPa with b = −0.134 fixed at the literature consensus value. Compared to the ANSYS library constants (σ'f = 2282 MPa, b = −0.134), the calibrated constants reduce predicted fatigue life by 55% across all load levels. The critical safe load threshold (safety factor SF = 1.0) shifts from 23.6 kN (library) to 21.2 kN (calibrated), a 10.2% reduction with direct design implications. The calibrated model is validated against three independent published experimental datasets for L-PBF IN625, showing improved agreement in the finite-life regime. These results establish that uncalibrated material library constants systematically overestimate L-PBF IN625 fatigue performance and provide quantitative guidance for safe load determination in fatigue-critical AM components.