The fatigue resistance of certain additively manufactured (AM) materials in machined surface condition, such as Ti-6Al-4V, is not only often inferior to that of their wrought counterparts but also associated with significant uncertainty. For example, fatigue strengths half of wrought materials and fatigue data scatter over one order of magnitude have been reported for laser powder bed fused (L-PBF) Ti-6Al-4V. The fatigue failure in such materials can almost always be traced back to one or a group of volumetric anomalies, including gas-entrapped pores, key holes, and lack-of-fusion defects. On one hand, they are stress risers and can significantly accelerate the initiation of fatigue cracks and shorten fatigue life in the mid and high cycle fatigue regimes, where crack initiation is more influential. On the other hand, the features of the volumetric defects, such as their size, shape, and location, can greatly vary due to the small perturbations in the processing conditions, which can significantly alter the stress field in the vicinity, which is responsible for the large fatigue data scatter. In the literature, although the critical role of volumetric defect is qualitatively acknowledged overall, the precise correlations between the defects’ features with fatigue behavior of AM materials are still lacking. This presentation provides a snapshot of current research efforts at the National Center for Additive Manufacturing Excellence (NCAME) to understand the defect criticality in fatigue behavior of L-PBF Ti-6Al-4V in the machined surface condition. A significant experimental campaign has been undertaken to characterize the fatigue behavior of this material, which has resulted in ~400 data points including fully characterized fracture surfaces. Combining data analytics and numerical modeling, the correlation between the geometric features of fatigue critical defects and the fatigue life is being established.