Purpose: The aim of this article was to demonstrate a novel approach to designing facial prostheses using the transplantation concept and computer-assisted technology for extensive, large, maxillofacial defects that cross the facial midline. Materials and Methods: The three-dimensional (3D) facial surface images of a patient and his relative were reconstructed using data obtained through optical scanning. Based on these images, the corresponding portion of the relative's face was transplanted to the patient's where the defect was located, which could not be rehabilitated using mirror projection, to design the virtual facial prosthesis without the eye. A 3D model of an artificial eye that mimicked the patient's remaining one was developed, transplanted, and fit onto the virtual prosthesis. A personalized retention structure for the artificial eye was designed on the virtual facial prosthesis. The wax prosthesis was manufactured through rapid prototyping, and the definitive silicone prosthesis was completed. Results: The size, shape, and cosmetic appearance of the prosthesis were satisfactory and matched the defect area well. The patient's facial appearance was recovered perfectly with the prosthesis, as determined through clinical evaluation. Conclusion: The optical 3D imaging and computer-aided design/computer-assisted manufacturing system used in this study can design and fabricate facial prostheses more precisely than conventional manual sculpturing techniques. The discomfort generally associated with such conventional methods was decreased greatly. The virtual transplantation used to design the facial prosthesis for the maxillofacial defect, which crossed the facial midline, and the development of the retention structure for the eye were both feasible.