Background and Objectives: We aimed to determine the link between brain volumetry results and functional disability calculated using the Expanded Disability Status Scale (EDSS) among multiple sclerosis (MS) patients in relation to the provided treatment (disease-modifying therapies (DMTs)) during a 5-year follow-up period.Materials and Methods: A retrospective cohort study was performed enrolling 66 consecutive patients with a confirmed diagnosis of MS, predominantly females (62% (n= 41)). Relapsing–remitting (RR) MS was noted in 92% (n= 61) of patients, with the rest being patients with secondary progressive (SP) MS. The mean age was 43.3 years (SD 8.3 years). All patients were evaluated clinically using the EDSS and “FreeSurfer© 7.2.0” radiologically during a 5-year follow-up.Results: A significant increase in patient functional disability was noted, calculated using the EDSS during a 5-year follow-up. The baseline EDSS ranged between 1 and 6 with a median of 1.5 (IQR 1.5–2.0), and after 5 years, the EDSS was between 1 and 7, with a median EDSS of 3.0 (IQR 2.4–3.6). Compared with RRMS patients, SPMS patients demonstrated a significant increase in EDSS score during a 5-year period, with a median EDSS of 2.5 in RRMS patients (IQR 2.0–3.3) and 7.0 (IQR 5.0–7.0) among SPMS patients. Significantly lower brain volumetry results in different brain areas were found, including cortical, total grey and white matter,p< 0.05. Statistically significant differences were observed between baseline volumetry results of the hippocampus and the middle anterior part of the corpus callosum and their volumetry results after 5 years,p< 0.001. In this study population, the thalamus did not demonstrate significant changes in volumetry results during follow-up,p> 0.05. The provided treatment (DMTs) did not demonstrate a significant impact on the brain MRI volumetry results during a 5-year follow-up,p> 0.05.Conclusions:Brain MRI volumetry seriously impacts the early detection of brain atrophic changes. In this study, significant relationship between brain magnetic resonance volumetry results and disability progression among MS patients with no important impact of the provided treatment was described. Brain MRI volumetry may aid in the identification of early disease progression among MS patients, as well as enrich the clinical evaluation of MS patients in clinical patient care.