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A crack growth-based multiaxial fatigue life prediction model is proposed in this paper, which uses a characteristic plane-based methodology for multiaxial fatigue damage analysis and the Equivalent Initial Flaw Size (EIFS) concept for life prediction. The orientation of the characteristic plane is theoretically determined by minimizing the damage contribution of the hydrostatic stress amplitude and correlates with the material local failure modes. An equivalent stress intensity factor under the general multiaxial load is proposed. The fatigue life is predicted by integration from the EIFS to the critical crack length. The proposed model can be used for fatigue life predictions of smooth specimens under both in-phase and out-of-phase loading conditions and can automatically adapt for different material failure mechanisms under various loading conditions. The fatigue life prediction results are validated with experimental data for a wide range of metallic materials available in the literature. It is shown that model predictions are in good agreement with experimental data under both proportional and nonproportional load.