With global demand for 3D printed medical devices on the rise, the search for safer, inexpensive, and sustainable methods is timely. Herein, we assessed the practicality of the material extrusion process for acrylic denture bases of which successful outcomes can be extended to implant surgical guides, orthodontic splints, impression trays, record bases and obturators for cleft palates or other maxillary defects. Representative materials comprising denture prototypes and test samples were designed and built with in-house polymethylmethacrylate filaments using varying print directions (PDs), layer heights (LHs) and reinforcements (RFs) with short glass fiber. The study undertook a comprehensive evaluation of the materials to determine their flexural, fracture, and thermal properties. Additional analyses for tensile and compressive properties, chemical composition, residual monomer, and surface roughness (Ra) were completed for parts with optimum parameters. Micrographic analysis of the acrylic composites revealed adequate fiber-matrix compatibility and predictably, their mechanical properties improved simultaneously with RFs and decreased LHs. Fiber reinforcement also improved the overall thermal conductivity of the materials. Ra, on the other hand, improved visibly with decreased RFs and LHs and the prototypes were effortlessly polished and characterized with veneering composites to mimic gingival tissues. In terms of chemical stability, the residual methyl methacrylate monomer contents are well below standards threshold for biological reactions. Notably, 5 vol% acrylic composites built with 0.05 mm LH in 0° on z-axis produced optimum properties that are superior to those of conventional acrylic, milled acrylic and 3D printed photopolymers. Finite element modeling successfully replicated the tensile properties of the prototypes. It may well be argued that the material extrusion process is cost-effective; however, the speed of manufacturing could be longer than that of established methods. Although the mean Ra is within an acceptable range, mandatory manual finishing and aesthetic pigmentation are required for long-term intraoral use. At a proof-of-concept level, it is evident that the material extrusion process can be applied to build inexpensive, safe, and robust thermoplastic acrylic devices. The broad outcomes of this novel study are equally worthy of academic reflection, and further translation to the clinic.