OBJECTIVE: The goal of this study is to understand the evolution of cognitive phenotypes in a clinical cohort of adult patients with relapsing-remitting multiple sclerosis (RRMS) over time and to assess whether demographic and clinical features of MS have any effect on the progression of cognitive decline in MS. METHODS: One hundred twenty-five patients with RRMS underwent annually neuropsychological assessment along 3 to 5 consecutive years with the brief repeatable battery of neuropsychological tests (BRBN-T) and the brief international cognitive multiple sclerosis (BICAMS). The international classification of cognitive disorders in multiple sclerosis (IC-CoDiMS) was used to define the cognitive phenotypes. RESULTS: In our cohort the mean age was 41.81 years and 88 patients (70.4%) were female. The prevalence of cognitive impairment decreased over the 3-year assessments, both in BRBN-T (29.6% vs. 25.0% vs. 18.5%) and BICAMS (33.6% vs. 30.4% vs. 19.2%). Longitudinal differences were observed for all the applied tests, except for verbal fluency, with the results pointing to an improvement in performance over time. At the first and the 3rd assessment, we observed four cognitive phenotypes: intact, uni-domain, bi-domain, and multidomain. At the 4th and 5th assessments, no patients presented multi-domain impairments. MS patients with optic neuritis (ON) as onset syndrome, showed the highest percentage of cognitive impairment on both BRBN-T and BICAMS. CONCLUSIONS: This study corroborates the importance of knowing the evolution of cognitive performance over time to better determine the best cognitive intervention programs in order to prevent cognitive decline and promote quality of life.