Previous infection with Epstein-Barr virus (EBV) and infectious mononucleosis are established multiple sclerosis (MS) risk factors, and elevated serum titers of anti-EBV nuclear antigen (anti-EBNA) antibodies in healthy adults are strongly correlated with future MS risk. In this prospective study, we investigated the association between EBV neutralizing antibodies and MS risk. MS risk tended to be higher in individuals with high titers of neutralizing antibodies compared to those with low titers (relative risk [RR] = 2.2, 95% confidence interval [CI] 0.97-5.1). This association was attenuated after adjustment for anti-EBNA1 IgG Ab titers (RR = 1.4, 95% CI 0.5-3.5). This preliminary finding warrants further study in a larger population.