Background: Many authors have reported on therapeutic strategies for traumatic optic neuropathy and their experience with endonasal endoscopic optic nerve decompression for traumatic optic neuropathy. However, to our knowledge, few have described the therapeutic strategies for nontraumatic optic neuropathy and navigation-assisted endoscopic optic nerve decompression as a treatment for nontraumatic, compressive optic neuropathy. The aim of this study was to examine the advantages in treating nontraumatic optic neuropathy with the minimally invasive, image-guided, navigation-assisted, endonasal endoscopic optic nerve decompression. Methods: This was a retrospective study of 20 patients (21 eyes) diagnosed with nontraumatic optic neuropathy, undergoing an endonasal endoscopic approach to relieve space-occupying lesions and decompress the optic nerve under image-guided navigation. This article describes our research on the therapeutic strategies for nontraumatic optic neuropathy patients, with special focus on the advantages of navigation-assisted, endonasal, endoscopic optic nerve decompression for the treatment of nontraumatic optic neuropathy. Medical photographs were used to estimate the status of the patients. Results: In 18 of the 20 cases, space-occupying lesions were completely resected. In two cases, they were partially resected. All 20 cases (21 eyes) underwent image-guided, navigation-assisted, endonasal endoscopic optic nerve decompression. Visual acuity improved in 20 eyes (95.2%) and remained stable in one eye. There were no intraoperative or postoperative complications. Conclusions: Optic nerve decompression is the main treatment strategy for nontraumatic optic neuropathy, to relieve space-occupying lesions and decompress the optic nerve, and to retain and/or improve visual acuity. Image-guided navigation can help doctors pinpoint the optic nerve when facing anatomical deformation caused by a space-occupying lesion. Navigation-assisted, endonasal endoscopic optic nerve decompression is a feasible, safe, practical, and minimally invasive approach. (C) 2019 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.