The purpose of this study was to illustrate how cognitive functioning evolves over time in patients with multiple sclerosis. We followed the evolution of cognitive performances in two clinically and demographically similar multiple sclerosis groups, the 'cognitively preserved' (n = 20) and the 'cognitively mildly deteriorated' (n = 22), and in healthy controls (n = 34). We conducted the follow-up examination using the Mild Deterioration Battery, the Mini-Mental State Examination, and a set of additional neuropsychological measures after an interval of 3 years. The drop-out rate in our study was only 5%. The 'cognitively preserved' multiple sclerosis group showed substantial neuropsychological stability by performing as well as the controls both at baseline and at follow-up. By contrast, the initially 'cognitively mildly deteriorated' group demonstrated progressive cognitive decline on many neuropsychological tests. The intermediate-length screening battery, the Mild Deterioration Battery, was sensitive to this decline, whereas the briefer Mini-Mental State Examination was not. The progressive cognitive decline could not be predicted from other disease variables. The study demonstrated that intact cognitive functioning in multiple sclerosis may remain stable, whereas incipient cognitive decline seems to be widespread and progressive in nature. Thus, progressive cognitive deterioration should be considered as one of the characteristics of multiple sclerosis.