Purpose: To evaluate the biomechanics of a novel implant placement distribution and compare it with that of conventional maxillary overdenture support using three-dimensional finite element analysis (FEA). The application of zirconia implants in the context of this novel design was also evaluated. Materials and Methods: Detailed FEA models were created to analyze the loading responses of two different distributions of implants to support maxillary overdentures. The two implant distributions were as follows: the conventional design (D1) included four unsplinted implants in the premolar regions, whereas the novel design (D2) included one midpalatal implant, bilateral canine/premolar implants, and one anterior off-center crestal implant. Anatomical models were created with computed tomographic data and static loads were applied axially and obliquely. Von Mises stresses and equivalent strains generated in peri-implant bone and first principal stresses in the implants were calculated, including any denture displacement. Results: Comparable stress and strain values were seen in the peri-implant bone for both designs. A significant decrease in the first principal stresses of D2 implants was observed with oblique loads. The maximum equivalent strain produced in the peri-implant region was mostly within the range for bone augmentation. D2 displayed lower maximum displacement values than D1. Maximum tensile stresses in the zirconia implants for either design were well below their fracture strength. Conclusions: A novel four-implant distribution involving midpalatal and crestal implants may be an alternative to the conventional design used for maxillary overdentures. This is particularly relevant when anatomical considerations prevent the placement of four anterior crestal implants. Zirconia implants may also be a valid option for a selected group of patients or for those requesting metal-free restorations. Prospective clinical studies are required to confirm these in vitro results.