Cognitive impairment (CIm) is a frequent finding in multiple sclerosis (MS) affecting up to 65% of patients. The aim of this study was to evaluate the prevalence and incidence of CIm in a population-based cohort of MS patients identified in the city of Catania from 1995 to 2004. One-hundred and twenty-five patients experiencing the onset of MS during 1995-2004 were enrolled. Cognitive performance was assessed through the Brief Repeatable Battery (BRB) of neuropsychological tests and the Stroop word-color task (ST). CIm was defined as the failure on at least three tests involving at least two different domains. Patients without CIm at baseline were followed up after over 3 years. The most impaired tests were the Symbol Digit Modalities Test (36%) and the Paced Auditory Serial Addition Test 3 (35%). At baseline the prevalence of CIm was 44% (95% CI 35.2-53.1). An almost sixfold increased risk of developing CIm was found among MS patients aged 40 and above at the time of the NPS examination (OR 5.84; 95% CI 2.57-13.2; p value <0.0001) and a threefold increased risk for patients with an EDSS score >3 (OR 3.51; 95% CI 1.30-9.46, p value 0.01). At the follow-up out of the 70 MS patients without CIm at baseline evaluation, 26 (37.1 %) developed CIm. The total person-years at risk was 269 person-years giving an incidence rate of CIm of 96.6/1,000 person-year (95% CI 57.3-128.7). The overall prevalence of CIm in MS is 44% and the incidence after 4 years is 37.1%. CIm affects more frequently patients older than 40 years and with a higher EDSS score.