Purpose: To test a novel implant metal-acrylic prosthesis design in comparison to a conventional prosthesis design through simulation of cyclic masticatory loading. The novel design involved digital designing and fabrication of the framework and the matched veneering acrylic resin material. Materials and Methods: Ten prostheses were fabricated for each group. All the prostheses exhibited a similar external design on two implants with a distal cantilever. The conventional group comprised a milled metal framework with mechanically retained acrylic denture teeth via vertical pins. The digital prosthesis group incorporated an inverted T-shape bar and a monolithic milled acrylic resin veneer. The resin veneer was subsequently adhesively attached on the bar. All prostheses were thermally aged and subjected to laboratory cyclic loading at the cantilever region. The load-to-failure and the number of cycles until failure were collected. Furthermore, failed specimens were analyzed to determine the mode of failure. Results: The digital prostheses failed at significantly greater load-to-failure (1,570.0 N ± 116.0 N) and number of cycles (124,857 ± 21,608) than the conventional prostheses (load-to-failure = 1,015.0 N ± 47.4 N; number of cycles = 28,452 ± 6,559). The conventional prostheses failed by fracturing of the acrylic teeth and veneering material that led to exposure of the metal framework. Half of the digital prostheses failed by superficial chipping of the veneering material, while the other half failed by the deformation and fracture of screws. Conclusion: Within the limitations of this study, the digital prostheses with the novel design and monolithic veneering material showed significantly higher strength compared with the conventional prostheses. The mode of acrylic failure of the digital prostheses was more favorable. Keywords: CAD/CAM, edentulous, full-arch, hybrid prosthesis, implant-fixed prosthesis, implants