We report follow-up data on the efficacy of natalizumab therapy on neuropsychological impairment on an italian MS group of 39 patients at 1 year and of 11 patients at 2 years. Results show a significant reduction in relapse rate, in the number of impaired neuropsychological tests as well as in several single executive function and reasoning tests scores at 1 year. Improvement persisted at 2 years, including also memory and speed processing tasks. These data support the efficacy of natalizumab therapy in all the clinical domains, including cognitive deterioration, in multiple sclerosis patients.