Objective To compare the differences of optic disc parameters and the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) in acute uveitis Vogt-Koyanagi-Harada (VKH) syndrome with different degrees of optic disc edema. Methods This is a retrospective study including 40 eyes of 23 VKH patients. The eyes were divided into 2 groups according to the results of fluorescein fundus angiography (FFA). The discs with hyperfluorescence but no leakage were in mild optic disc edema group (group A, 13 patients and 25 eyes), and the discs with hyperfluorescence and leakage were in severe optic disc edema group (group B, 10 patients and 15 eyes). The patients were significantly older in group B than in group A (t=−2.17, P＜0.05). The differences of gender, diseased time (t=−1.67) and corrected visual acuity (t=−0.76) between 2 groups were not significant (P＞0.05). Eighty eyes of 46 normal healthy subjects, matching group A and group B with age and gender, were divided into group C (26 subjects and 50 eyes) and group D (20 subjects and 30 eyes) respectively. All subjects underwent three dimensional optical coherence tomography examinations. 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. Results The disc area, disc cup area and rim area were bigger, the thickness of mean CP-RNFL and the nasal and temporal quadrants of CP-RNFL were thicker in group A than those in group C (P＜0.05). The disc area and rim area were bigger, the thickness of mean CP-RNFL and the nasal, superior, temporal and inferior quadrant of CP-RNFL were thicker, C/D area ratio and C/D diameter ratio were smaller in group B than those in group D (P＜0.05). The disc area was bigger, disc cup area, C/D area ratio and C/D diameter ratio were smaller, the thickness of mean CP-RNFL and the nasal , superior and inferior quadrants of CP-RNFL were thicker in group B than those in group A (P＜0.05). Conclusions Acute VKH uveitis with mild optic disc edema has thicker CP-RNFL in the nasal and temporal quadrants; with severe optic disc edema has thicker CP-RNFL in all 4 quadrants. Acute VKH uveitis also has smaller C/D area ratio and C/D diameter ratio.