The identification of predictive factors of NAbs development might have a relevant impact on clinical practice. Our objective is to look after predictive factors of NAbs development in MS IFN Beta-1b-treated patients. Database was screened for patients on IFN Beta-1b treatment with an Expanded Disability Status Scale (EDSS) at a baseline between 1 and 3.5, disease duration shorter than 15 years, and NAbs analysis performed every 6 months. The NAbs positive status was analysed in relation to baseline clinical, neuropsychological and brain imaging measures. Forty-nine patients were included. Sixteen patients had become NAbs positive at some point on IFN therapy (35%). NAbs producers differed from not producers for higher incidence of cognitive deficit and higher lesion load (OR = 5.0 and 5.6, respectively). Our study suggests that NAbs development might be a marker of a more aggressive disease and that worse outcome in NAbs producers might be biased by baseline condition.