['Demyelinating events in relapsing-remitting multiple sclerosis (RRMS) can involve several locations in the central nervous system. We sought to determine if initial clinical demyelinating event (IDE) location predicts subsequent clinical relapse locations in early RRMS.', 'We identified all RRMS patients from two large MS clinics who were seen within 1 year of disease onset. Logistic regression was performed with the outcome defined as the second or third exacerbation location and the predictor defined as IDE+/-second event location.', "195 patients with at least two clinical exacerbations were identified. There was an increased odds of a patient's second relapse occurring in the spinal cord if the IDE was in the spinal cord (odds ratio (OR) = 3.79, 95% CI 2.06 to 7.00, p<0.001). There was more than a sixfold increase in the odds of a patient's second relapse occurring in the optic nerve if the IDE was in the optic nerve (OR = 6.18, 95% CI 2.90 to 13.18, p<0.001). These associations remained similar after adjusting for treatment and patient characteristics. If the IDE and second event were both in the same location (spinal cord, optic nerve or brainstem/cerebellum), the third event was likely to remain in that location."] Does the onset location of multiple sclerosis predict the location of subsequent relapses?