INTRODUCTION: MS is an autoimune demyelinating and neurodegenerative disease of the central nervous system which predominantly affects young working population, especially women of generative age. During the last 15 years significant progress in treatment options for this disease has been made, and now more than ever, there is a geat need for relible disease course prediction factors. Studies indicate that one of the more important prediction factors is the presence of brainstem lesions on MRI. The aim of this study is to evaluate the role of a combination of standard EP modalities and newer neurophysiological methods for brainstem function evaluation (i.e. VEMP and SSEP of the tongue) in predicting the progression of the disease in people with CIS, the first clinical presentation of MS. ----- METHODS: Altogether 121 subjects with CIS diagnosis were included in the study. All the subjects included in the final analysis were followed-up for at least two years. Upon study inclusion the following data were obtained: EDSS, total number of T2 lesions, MSFC, VEP, BAEP, SSEPm, SSEPt, VEMPo, VEMPc and SSEPj. Results of all of the EP modalities were expressed in the form of a single EP score. During the two-year follow-up period patients were controlled in 6-month intervals, and the following data regarding MS activity were obtained at each of the follow-up visits: EDSS, SAD, occurrence of a new relapse, new T2 lesions on MRI or worsening of MSFC. ----- REZULTS: After a two-year follow-up period all the data on MS activity and progression was obtained for 94 patients which were included in the final analysis. The multivariable regression model including age, sex, total number of T2 lesions on baseline MRI, and EP score >13 showed that total number of T2 lesions on baseline MRI and EP score >13 increase the likelihood for sustained accumulation of disability (SAD). After controlling for age, sex, total number of T2 lesions on baseline MRI, the hazard of SAD for participants with EP score >13 is 4.093 times that of participants with EP score ≤13. EP score >13, also increases the likelihood for progression measured with the composite measure of progression which uses EDSS, 9HPT and T25FWT (Exp(B)=5.577, 95% CI=1.520-20.468, p=0.01). Multivariate regression analysis results using EP score calculated without VEMP and SSEPj results did not show statistical significance in SAD predicting. ----- CONCLUSION: The results indicate that the EP score is a good tool for predicting the disease progression in CIS patients over a relatively short follow-up period of two years. VEMP and SSEPj were found to be crucial in achieving EP score's predictive significance, thereby justifying their inclusion in this score.