Customized one-component dental implants have been fabricated using Electron Beam Melting® (EBM®), which is a rapid prototyping and manufacturing technique. The goal of our study was to determine the effect of electron beam orientation on the fatigue resistance of EBM Ti-6Al-4V ELI alloy. EBM technique was used to fabricate Ti-6Al-4V ELI alloy blocks, which were cut into rectangular beam specimens with dimensions of 25 × 4 × 3 mm, such that electron beam orientation was either parallel (group A) or perpendicular (group B) to the long axis of the specimens. The specimens were subjected to cyclic fatigue (R = 0.1) in four-point flexure under ambient conditions using various stress amplitudes below the yield stress. The fatigue lifetime data were fit to an inverse power law–Weibull model to predict the peak stress corresponding to failure probabilities of 5 and 63% at 2M cycles (σmax, 5% and σmax, 63%). Groups A and B did not have significantly different Weibull modulus, m (p > 0.05). The specimens with parallel orientation showed significantly higher σmax, 63% (p ≤ 0.05), but there was no significant difference in the σmax, 5% (p > 0.05). Thus, it can be concluded that the fatigue resistance of the material was greatest when the electron beam orientation was perpendicular to the direction of crack propagation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 124–130, 2013.