Traditionally, metal-ceramics, metal-reinforced acrylics, and—more recently—full-contour or layered zirconia have been the materials of choice for definitive fixed implant-supported rehabilitations. Polymethyl methacrylate (PMMA) is commonly used in implant dentistry for the fabrication of implant-supported interim prostheses and as milled or 3D-printed prototypes. This article describes a novel protocol to prosthetically restore a completely edentulous patient following a digital workflow, with fixed, screw-retained, implant-supported prostheses fabricated from CAD/CAM milled PMMA, with no metal substructure. After a 2-year follow-up in terms of esthetics, phonetics, function, and biologic tissue response, the outcome remains functional and free of mechanical, biomechanical, or biologic complications. The aim of this article is to illustrate the feasibility of using milled PMMA as a viable definitive prosthetic material for the fixed implant rehabilitation of edentulous patients.