The authors present a retrospective review of individuals diagnosed with either neuromyelitis optica spectrum disorder (NMOSD) or multiple sclerosis (MS). The aim of the study was to assess the prevalence of internuclear ophthalmoplegia (INO) in both groups over a 10-year period at two hospital sites. This included if the diagnosis was given at the initial presentation or developed subsequently during the follow-up period. The study required all cases to be identified or confirmed by a neuro-ophthalmologist. A total of 280 individuals were included in the study, with a larger proportion of 200 having a diagnosis of MS. Some differences in the demographic make-up of the two groups were identified including race, history of optic neuritis and transverse myelitis. A large proportion of both groups were on disease-modifying treatment. The prevalence of INO within the MS group was reported as 16% versus NMOSD as 1.3%. Using logistic regression, the authors report INO is 14 times less likely to occur in NMOSD than MS at any time point independent of a range of demographic characteristics. A limitation to the study is the low numbers of myelin oligodendrocyte glycoprotein (MOG) associated disease preventing subgroup analysis. The authors hypothesise that with a larger study it would be possible to stratify NMOSD by sero-status. The prevalence reported of INO in MS in this study is at the low end of the range compared to other literature. An unexpected finding in this study was the different racial composition of the two groups. This study indicates that medial longitudinal fasciculus lesions are less common in NMOSD. Clinically the diagnosis of INO could support differential diagnosis and allow for earlier provision of appropriate treatment.