Purpose: According to the so-called All-on-Four protocol, four dental implants are placed in the interforaminal region of the edentulous mandible to support full-arch fixed prostheses. In this design, the posterior implants are tilted distally to a maximum of 45 degrees. The purpose of this finite element study was to evaluate the stress concentration in peri-implant bone during two loading conditions and to compare this design with another design in which the four implants are placed parallel to each other and perpendicular to the occlusal plane. Materials and Methods: Three-dimensional finite element models consisted of mandibular bone, four dental implants inserted in two different configurations-with the distal implants tilted (model A) or four parallel implants (model S)-and hybrid superstructures. Two loading conditions (178 N/central incisors or 300 N/left first molar) were considered, and von Mises stress values were determined. Results: During anterior loading, higher stress concentrations were detected in the peri-implant bone of all four implants in model A. During posterior loading, lower stress concentrations were observed around the anterior implants of model A; however, the tilted posterior implants were subjected to higher stresses in every condition. Conclusions: Application of either of these designs was successful in reducing peri-implant stress in one loading condition. However, neither design demonstrated better performance in both loading conditions; therefore, within the limitations of this study, neither design demonstrated clearly superior performance. Keywords: All-on-Four, edentulous mandible, finite element analysis, tilted implant