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Additive manufacturing (AM) refers to advanced technologies for building 3D objects by adding material layer upon layer using either electron beam melting (EBM) or selective laser melting. AM allows us to produce lighter and more complex parts. However, various defects are created during the AM process, which severely affect fatigue behavior. In the current research, the effects of the anisotropic microstructure in the in-plane and out-of-plane orientations and defects on the fatigue crack propagation rate (FCPR) and crack path were studied. A resonance machine was used to determine the fatigue crack propagation rate (da/dN vs. ΔK) from the near-threshold up to the final fracture, accompanied by in situ Acoustic Emission (AE) monitoring. Micro-Computerized Tomography (µCT) enabled us to characterize surface and microstructural defects. Metallography was used to determine the microstructure vs. orientations and fractography to classify the fatigue fracture propagation modes. Calculations of the local stress distribution were performed to determine the interactions of the cracks with the defects. In the out-of-plane direction, the material exhibited high fatigue fracture toughness accompanied by a slightly lower fatigue crack propagation rate as compared to in-plane orientations. The near-threshold stress intensity factor was slightly higher in the out-of-plane orientation as compared to that in the in-plane one, accompanied by a lower exponent of the Paris law regime. The threshold decreased with an increasing load ratio as expected for both orientations. The crack propagation direction that crosses the elongated grains plays an important role in increasing fatigue resistance in the out-of-plane direction. In the in-plane directions, the crack propagates parallel to the grain boundary, interacts with more defects and exhibits more brittle striations on the fracture surface, resulting in lower fatigue resistance. [ABSTRACT FROM AUTHOR]