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Objective  Temporalis muscle flap (TMF) is widely used in traditional skull base surgery, but its application in endoscopic skull base surgery remains rarely reported. We aimed to investigate the surgical anatomy and clinical application of TMF for reconstruction of skull base defects after expanded endoscopic nasopharyngectomy. Methods  Nine fresh cadaver heads (18 sides) were used for endoscopic dissection at the University of Pittsburgh School of Medicine in the United States. TMF was harvested using a traditional open approach and then transposed into the maxillary sinus and nasal cavity through the infratemporal fossa using an endoscopic transnasal transmaxillary approach. TMF length was then measured. Moreover, TMF was used for the reconstruction of skull base defects of six patients with recurrent nasopharyngeal carcinoma after expanded endoscopic nasopharyngectomy. Results  The length of TMF harvested from the temporal line to the tip of the coronoid process of the mandible was 11.8 ± 0.9 cm. The widest part of the flap was 9.0 ± 0.4 cm. When TMF was dislocated from the coronoid process of the mandible, approximately another 2 cm of reach could be obtained. When the superficial layer of the temporalis muscle was split from the deep layer, the pedicle length could be extended 1.9 ± 0.2 cm. TMF could cover skull base defects in the anterior skull base, sellar, and clivus regions. Conclusion  TMF can be used to reconstruct skull base defects after endoscopic expanded nasopharyngectomy and can effectively prevent the occurrence of serious complications in patients with recurrent nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]