© 2021 Ariesdue. All rights reserved.Aim The present in vitro study aimed to evaluate the effect of different dental implant macrodesigns on the stress occurred on the implants and bone for two-implant-supported overdentures (IOD) in the rehabilitation of edentulous mandibles. Methods Six different implant brands and macro design were used in this study. Two groups, Group V (V-thread shape) and Group R (reverse buttress thread shape), were formed based on implant thread shape. Vertical and oblique loads were applied to the implants in order to evaluate tension, compression, and Von Mises stresses by implementing the three-dimensional finite element analysis. Results According to the stresses after the applied forces, the macrodesign of dental implants affects stress distribution in different directions. Group R exerted more stresses on the cortical bone, while Group V produced more stresses on the implants. Tissue level implants caused high stresses on bones and low stress on itself. As proposed, microthread neck design decreased the stresses on the cortical bone. Conclusion In the light of these biomechanical findings, considering the anterior region of the mandible often consists of dense cortical bone, it may be advantageous to prefer implants with a V-thread design and a microthread neck surface, which creates less stress in the cortical bone.