Purpose:.To analyze clinical features and main causes of multiple sclerosis-related optic neuritis (MS-ON), providing evidence for the differential diagnosis of MS-ON. Methods: Clinical data were collected from 527 patients, 123 males and 404 females, diagnosed with MS-ON between June 2008 and June 2013. Visual acuity, optometry, visual field, slit-lamp microscopy, indirect ophthalmoscopy (20D), opti-cal coherence tomography (OCT) and magnetic resonance imaging (MRI) were performed. Venous blood was sampled for detection of autoimmune antibodies and Aquaporin (AQP-4). Results:.Fifty nine cases were diagnosed with neuromyelitis optica-related optic neuritis. (NMO-ON),.27 Sjogrens syn-drome-related optic neuropathy,.22 tumors,.21 anterior is-chemic optic neuropathy, 15 radiation-induced optic neuropa-thy, 14 optic neuropathy-related infection, 17 genetic eye dis-eases and 10 open angle glaucoma. Among168 MS-ON pa-tients undergoing optic nerve MRI,90 cases (53.57%) had a lesion 30 mm in two (1.19%). Conclusion:.MS-ON is more commonly misdiagnosed with NMO-ON and Sjogrens syndrome, when compared to optic neuropathy, tumors and ischemic optic neuropathy.