Background Peripapillary retinal nerve fiber layer thickness correlates with radiological and clinical parameters in patients with MS. Objective The aim of this study is to investigate the use of the first measured pRNFL thickness as a predictor of disease course in patients with RRMS. Methods One hundred and thirty seven RRMS patients were enrolled in the study within the first 5 years of illness. Patients were followed for 34.1 months and the EDSS was used to assess disability status to determine whether the first measured pRNFL thickness, using proportional hazards models, predicts the risk of disability worsening. Results The mean disease duration was 26.1 months. Disability worsening was detected in 36 patients. In tertile-based groups formed according to pRNFL thickness, the group with the lowest pRNFL thickness had a 2.8-fold increase in the risk of disability worsening compared to the group with the highest. The risk was higher in the first 2 years of the study (HR = 3.48; p = 0.008). Conclusion The first measured pRNFL thickness in RRMS patients can predict the risk of disability worsening, and the risk of disability worsening in the early period was higher in the group with the lowest pRNFL value.