Purpose: The purpose of this study was to compare the stress and strain occurring in peri-implant bone and implants used to support maxillary overdentures. Three-dimensional finite element analysis (3D FEA) was used to compare one-piece zirconia and titanium implants. Materials and Methods: Two types of implants were simulated using a 3D FEA model: one-piece zirconia and titanium implants (diameter, 3.8 × 11.5 mm) with 2.25-mm diameter ball abutments. In each simulation four implants were placed bilaterally in the canine/premolar region of an edentulous maxillary model. Static loads were applied axially and 20 degrees buccolingually on the buccal slope of the lingual cusps of posterior teeth of the first quadrant. Von Mises stresses and equivalent strains generated in peri-implant bone and first principal stresses in the implants were calculated. Results: Comparable stress and strain values were shown in the peri-implant bone for both types of implants. The maximum equivalent strain produced in the peri-implant region was mostly within the range for bone augmentation. Under oblique loading, maximum von Mises stresses and equivalent strain were more evident at the neck of the most distal implant on the loaded side. Under axial load, the stress and strain were transferred to the peri-implant bone around the apex of the implant. Maximum tensile stresses that developed for either material were well below their fracture strength. The highest stresses were mainly located at the distobuccal region of the neck for the two implant materials under both loading conditions. Conclusions: From a biomechanical point of view, ceramic implants made from yttrium-stabilized tetragonal polycrystalline zirconia may be a potential alternative to conventional titanium implants for the support of overdentures. This is particularly relevant for a select group of patients with a proven allergy to titanium. Prospective clinical studies are still required to confirm these in vitro results. Different simulations presenting various cortical bone thicknesses and implant designs are required to provide a better understanding of the biomechanics of zirconia implants.