Background: Alloplastic temporomandibular joint (TMJ) replacement is a well-established procedure in maxillo-facial surgery. However, the surgical management of large excision in this area requires complex reconstruction beyond the standard TMJ prosthesis.Objective: This study aims to describe the design and the consequential application of a protocol which involves the use of computer-assisted surgery tools to best face complex TMJ reconstruction (TMJR). Preoperative accurate study of every single case and intraoperative check of the surgical act are nowadays essential to perform such delicate surgical procedures.Materials and Methods: The study is a retrospective and single institution case series. The various processes of the management and planning of extended TMJ reconstruction (eTMJR) are extensively described, from the preoperative clinical evaluation, imaging acquisition protocols and virtual surgical planning (VSP), focusing also on the intraoperative transfer of VSP using navigation and surgical guides.Results: We included nine patients with different pathologies which were candidates for eTMJR. Overall, the application of our protocol and workflow permitted the reduction of complications and pain, and the improvement of the maximum interincisal opening (MIO) of the patients, restoring patients’ masticatory function and esthetics.Conclusions:The eTMJR should be considered as a safe and reliable surgical management modality in selected patients with large temporomandibular joint and skull base (TMJ-SB) lesions. An accurate preoperative protocol and workflow is essential to perform such insidious and complex reconstruction. However, more extensive studies on this type of device have to be conducted in order to validate its real usefulness and indications.