Objective To compare the differences of optic disc morphology and optic nerve head parameters between Vogt-Koyanagi-Harada (VKH) syndrome and optic neuritis (ON) with optic disc edema. Methods This is a retrospective study including 21 first-onset VKH patients (35 eyes) as VKH group and 22 first-onset ON patients with optic disc edema (27 eyes) as ON group. The differences of age (t=-1.11) and gender (χ2=0.20) between two groups were not significant (P>0.05). Sixty-two eyes of 43 age and gender-matched healthy subjects were enrolled in this study as control group. All subjects underwent three dimensional optical coherence tomography (3D-OCT) examinations. The difference of optic disc morphology between two groups was observed. The parameters included average thickness of entire circumpapillary retinal nerve fiber layer (CP-RNFL), thickness of nasal, superior, temporal and inferior quadrant of CP-RNFL, disc area, disc cup area, rim area, cup/disc (C/D) area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio. The disc retinal pigment epithelium (RPE) angle was observed too. Results Among 35 eyes in VKH group, 31 eyes (88.57%) had retinal detachment next to the disc, 3 eyes (8.57%) had serrated inner limiting membranes of the disc. Twenty eyes (64.52%) had highly reflective points, lines, or membrane-like structures in the retinal detachment areas. No such signs appeared in ON patients. Compared with ON group, the optic cup area, C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio were bigger, the thickness of mean CP-RNFL and the superior, inferior quadrants of CP-RNFL were thinner, disc RPE angles was smaller in VKH group (P<0.05). Compared with control group, the disc area, optic cup area, rim area were bigger, C/D vertical diameter ratio was smaller, the mean CP-RNFL and 4 quadrants CP-RNFL were thicker, disc RPE angles was smaller in VKH group (P<0.05); the disc area, optic cup area, C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio were smaller, the mean CP-RNFL and 4 quadrants CP-RNFL were thicker, disc RPE angles was bigger in VKH group (P<0.05). Conclusions VKH patients have smaller disc RPE angles and more chance to develop retinal detachment next to disc than ON patients. The C/D area ratio, C/D horizontal diameter ratio and C/D vertical diameter ratio are bigger, the mean CP-RNFL and the superior, inferior quadrants of CP-RNFL are thinner in VKH eyes.