The aim of this study was to evaluate the effect of the All-on-4 design and 4 alternative implant-supported fixed prosthesis designs on stress distribution in implants, peri-implant bone, and prosthetic framework in the edentulous mandible under different loading conditions using three-dimensional finite element analysis (3D-FEA).Five different experimental finite element models (Model A (unsplinted 6), Model B (splinted 6), Model C (All-on-4), Model D (axial; 2 anterior, 2 posterior), and Model E (4 interforaminal)) were created. Three different loading conditions were applied (canine loading, unilateral I-loading, and unilateral II-loading). The highest minimum (Pmin) and the maximum (Pmax) principal stress values were acquired for cortical and trabecular bones; the highest von Mises (mvM) stress values were obtained for implants and metal frameworks. Model B and Model D showed the most favorable stress distribution. The All-on-4 design (Model C) also showed acceptable stress values close to those of Model B and Model D in the cortical and trabecular bones. In accordance with the stress values in the bone structure, the lowest stress values were measured in the implants and Co-Cr framework in Model B and Model D. The highest stress values in all structures were measured for unilateral loading- II, while the lowest values were found for canine loading. It was concluded that Model B and Model D experimental models showed better biomechanical performance in all structures. Furthermore, the use of a splinted framework, avoiding cantilevers, results in lower stress transmission. On the other hand, canine loading and unilateral loading-I exhibited the best loading conditions.