Purpose: The aim of this study was to evaluate the effect of implant inclination and cantilever length on the stress distribution in mandibular cortical bone, implant, abutment, prosthetic framework, and prosthetic screw via three-dimensional (3D) finite element analysis (FEA). Materials and Methods: Four different finite element models (0-0, 17-17, 30-30, 45-30) were designed according to the tilting angle (0, 17, 30, and 45 degrees) of the posterior implant and angle of multiunit abutments (0, 17, and 30 degrees). Screw-retained fixed prostheses with different cantilever lengths in accordance with implant inclination were modeled. A foodstuff was used for the 100-N load application. Maximum principal (Pmax) and minimum principal (Pmin) stresses were calculated for cortical bone, and von Mises stress values were calculated for the implant, abutment, metal framework, and prosthetic screw. Results: The highest stress values were observed in the anterior implant, surrounding bone, and prosthetic components of the 0-0 configuration. Pmin stress values in bone were gradually decreased with the increasing inclination of both anterior and posterior implants. Peak Pmax stress values were detected in the 0-0 group. For the cortical bone around the posterior implant, the 30-30 group showed the lowest Pmax value. The highest von Mises stress on implants was found at the posterior implant of the 30-30 group. The stress values on abutments gradually decreased with the increase of the angulation of the posterior implants. For prosthetic screws, the 30-30 and 45-30 groups exhibited lower stress values, and for the metal framework, the 30-30 group exhibited lower stress values. Conclusion: Biomechanical comparison via 3D FEA revealed that decreasing the cantilever length by tilting the posterior implants resulted in a reduction in stress values in the peri-implant bone, abutment, prosthetic screw, and metal framework. The groups with 30- and 45-degree tilted posterior implants and shorter cantilever lengths showed better stress distributions in comparison to the straight and 17-degree tilted groups. Keywords: All-on-4, edentulous mandible, finite element analysis, multiunit abutments, stress distribution, tilted implants