Purpose: To evaluate the performance of a computer-aided three-dimensional planning protocol in combination with previously inserted reference mini-implants and CAD/CAM technology to restore completely edentulous patients. The study evaluated implant and superstructure survival in a prospective clinical trial. Materials and Methods: The plan protocol called for treatment of 35 patients who were edentulous in either arch. Miniimplants were used to establish a platform for computed tomography and fixation of the surgical template. The planning software based on three-dimensional simulation was used to plan ideal implant placement, digitally integrating the future prosthetic and anatomical situations to design the definitive superstructure. Results: A total of 35 patients, 20 with edentulous maxillae, 10 with edentulous mandibles, and 5 patients with edentulism in both arches were treated. All patients received definitive prostheses on the day of surgery. The majority of patients treated in maxilla underwent a sinus graft procedure to achieve sufficient bone to place implants. A total of 40 superstructures were inserted and immediately loaded. Of the 240 inserted implants, 229 (95.4%) survived, with 146 (93.6%) and 83 (98.8%) implants in the maxillary and mandibular arches, respectively. Of the 10 implants that failed in the maxilla, 9 occurred in patients with an augmented sinus. All definitive restorations demonstrated clinically acceptable fit. Conclusions: When evaluating implant and superstructure survival, reference-based guided surgery seems to be a reliable treatment option for edentulous patients. The CAD/CAM superstructure, inserted and loaded immediately after guided implant insertion, demonstrated acceptable fit to the underlying implants. Keywords: computed tomography, computer-assisted surgery, dental implant, edentulism, surgical guide, surgical template, three-dimensional planning