Objectives: Cognitive impairment can be demonstrated in 40 to 65% of MS patients, starting from early stages. The aim of this study was to investigatealteration in cognitive impairment during long-term follow-up and the association with the disease characteristics. Method: Twenty-five MS patients (15 men, 10 women) were reexamined after an average of 5.3 years (range: 4.9-5.8). The disease duration, type, Expanded Disability Status Scale (EDSS) scores at the initial and last evaluations were recorded. They underwent a comprehensive neuropsychological evaluation. Major depression was excluded. Results: The mean age of the patients was 39.2±9.3 years and the mean duration of the disease was 11.4±5.14 years. The mean EDSS score at the beginning and last follow- up were 2.92±1.52 and 3.56±1.92, respectively. At the end of the follow-up period, the patients performed poorly on the Corsi Block-Tapping Test (p<0.001) and there was a significant difference in maximum word line in the verbal memory processes test (VMPT) (p<0.001). Short-term memory scores, assessed with the Wechsler Memory Scale (WMS), decreased slightly, but the total recall score was significantly worse (p<0.001). There was also significant decrease in executive functions according to the stroop test (p<0.001), and the Wisconsin Card Sorting Test (WCST) results in patients with a longer disease course were worse. Besides, there was a trend for worsening in the clock-drawing test. The language skills were well preserved. Patients with a disease duration of &#8805;10 years scored worse on the stroop test, clock-drawing test, Benton Line Orientation Test (BLOT), WCST, and VMPT.Discussion: The cognitive deficits tended to worsen during long-term follow-up. There was no correlation between severity of disability and cognitive impairment. However, there seems to be an association between results of some tests and disease duration.