To compare spatial patterns of cortical thickness alterations in neuromyelitis optica (NMO) and multiple sclerosis (MS); and to investigate the correlations between cortical thinning and clinical variables in NMO and MS. We studied 23 patients with NMO, 27 patients with MS and 26 healthy controls (HCs). The global, brain region and vertex-based cortical thickness (CTh) were analysed and compared among the three groups. A general linear model was used to investigate the correlations between cortical thinning and clinical measures. A limited number of cortical regions in visual cortex were found to be significantly thinner in NMO patients than in HCs. The MS patients exhibited more widespread cortical thinning compared with HCs, and significantly greater cortical thinning in the insula and the parahippocampus compared with NMO. The extent of cortical thinning in several brain regions correlated with cognitive measures in MS, but not in NMO. Neocortical thinning in NMO mainly affects visual cortex, while MS patients show much more extensive cortical thinning. Cognitive changes are correlated with cortical atrophy in MS not in NMO. The substrates of cognitive changes in MS and NMO could therefore be different. aEuro cent MS patients show much more extensive cortical thinning than NMO. aEuro cent Cortical thinning of insula and parahippocampus particularly distinguishes MS from NMO. aEuro cent Cognitive changes are correlated with cortical atrophy in MS but not in NMO.