© 2020 American Association of Oral and Maxillofacial Surgeons Purpose: Historically, synthetic polymers, such as polyamide, have been the predominate material used for patient-specific cutting guides in 3-dimensionally guided craniomaxillofacial surgery. The physical properties of polyamide result in guides that are bulky and difficult to place within the confines of the facial soft tissue envelope, requiring larger incisions with resultant morbidity. Despite their utility, we found the need for wider exposure simply for guide placement was unacceptable. The purpose of the present study was to evaluate our experience with the newly marketed titanium alloy cutting guides. Materials and Methods: We conducted a retrospective cohort study of patients who had undergone either segmental mandibulectomy or maxillectomy using patient-specific titanium alloy cutting guides from May to December 2019. The primary outcome variable was the need for an extended-access cervical incision or a transfacial incision for either maxillectomy or segmental mandibulectomy in patients with benign disorders. The secondary outcome variables included the need for a transfacial incision in patients with malignant pathology requiring either maxillectomy or composite oromandibular resection and the final histopathologic bone margin status. Results: Of the 21 included patients, 11 had undergone maxillectomy (1 of 2) or segmental mandibulectomy (9 of 9) for benign disorders, with 91% (10 of 11) having undergone titanium alloy guide placement and resection entirely transorally without the need for an extended cervical or a transfacial incision. For 10 of the 11 patients undergoing immediate reconstruction with vascularized bone flaps, transcervical access was limited to small 1.5- to 2.5-cm incisions for target vessel access and microvascular anastomosis. None of the 10 patients with a malignant disorder requiring either maxillectomy or composite oromandibular resection required a transfacial incision. The bone margins, as determined by histopathologic analysis, were negative for 100% of the patients. Conclusions: Patient-specific titanium alloy cutting guides represent a viable alternative to traditional synthetic polymer guides. Their superior properties permit easier intraoral placement, decreasing the need for cutaneous incisions and excessive periosteal stripping.