Aim: The aim of the study was to emphasize the prognostic value of the first five years of the natural course of multiple sclerosis for the disability progression, and a comparison of the relapsing-remitting and the primary progressive disease course. Material and methods: Using the retrospective design, we have evaluated the first five years of multiple sclerosis in the affected residents of the Kujawsko-Pomorskie district, treated at the Department of Neurology between July 2014 and September 2015. We have assessed the relationships between the Expanded Disability Status Scale score after the first five years of the disease and the clinical course, gender, initial symptoms, age at first symptoms, first magnetic resonance imaging data, cumulative relapse number in the first two or five years of the disease. Results: The investigated group consisted of 129 patients: 97 with the relapsing-remitting and 32 with the primary progressive disease course. The mean patients’ Expanded Disability Status Scale score after 5 years of the relapsing-remitting disease course was 2.1 ± 1.2. The mean number of relapses in the first two and five years in this subgroup was 2.2 ± 1.2 and 4.2 ± 2.5. The mean patients’ Expanded Disability Status Scale score after 5 years of the primary progressive disease course was 4.1 ± 1.4. A progression to Expanded Disability Status Scale score ≥3 in the period of evaluation was predicted by the primary progressive clinical course, older age at first symptoms, and more than five relapses in the first five years from the disease onset. Conclusions: This study confirms that early clinical differences of the natural course of multiple sclerosis could be strong predictors for moderate disability.