A fatigue life prediction method was introduced. The method was based on the combination of time domain and frequency domain method. Dynamic model of a complete railway locomotive system was established using SIMPACK software. The dynamic load histories acting on the bogie frame can be obtained by the Multi-Body System (MBS) analysis technique with time integration. FEM model of the bogie frame was established by applying ANSYS software. The natural frequencies and mode shapes of the frame were calculated and the dangerous nodes in the critical location were determined using the modal analysis technique. The stresses in dangerous nodes were calculated with the quasi-static stress/strain technology. PSD of the stresses was generated using the Fast Fourier Transformation (FFT). Fatigue life of the bogie frame was evaluated with the Dirlik’s formulation. Results showed that the calculated life of the analyzed bogie frame could meet the design requirement.