Applying four anterior implants placed vertically or tilted in the mandible is considered to provide clinically reasonable results in the treatment of mandibular posterior edentulism. It is also reported that a combination of four anterior and two short posterior implants can be an alternative approach for the rehabilitation of severe atrophy cases. In this study, we aimed to evaluate the biomechanical responses of three different implant placement configurations, which represent the clinical options for the treatment of mandibular edentulism. Three-dimensional models of the mandible, prosthetic bar, dental implant, abutment, and screw were created. Finite element models of the three implant configurations (Protocol 1: Four anterior implants, Protocol 2: Four anterior and two short posterior implants, Protocol 3: Two anterior and two tilted posterior implants: All-on-4 (TM) concept) were generated for 10 patients and analyzed under different loading conditions including chewing, biting, and impact forces. Protocol 2 led to the lowest stress concentrations over the mandible among the three protocols (p< 0.016). Protocol 2 resulted in significantly lower stresses than Protocol 3 and Protocol 1 over prosthetic bars under chewing forces (p< 0.016). None of the implant placement protocols consistently exhibited the lowest stress distribution over abutments. The lowest stresses over dental implants under the chewing, biting, and impact forces were obtained in Protocol 1, Protocol 2, and Protocol 3, respectively (p< 0.016). Protocol 3 was the best option to obtain the lowest stress values over the screws under all types of loading conditions (p< 0.016). In conclusion, Protocol 2 was biomechanically more ideal than Protocol 1 and Protocol 3 to manage the posterior edentulism.