Background. The disease‑free status defined in terms of NEDA‑3 parameter is increasingly used in clinical practice as a treatment goal in the therapy of multiple sclerosis (MS). The aim of the study was to evaluate the effect of the first line drugs on the persistence of NEDA‑3 status in patients with relapsing‑remitting MS. Methods. A retrospective study included a group of 222 patients with relapsing‑remitting multiple sclerosis treated with the first line drugs in the Multiple Sclerosis Center at the Neurological Department of the Military Medical Institute in 2010–2017. Results. In more than half of the patients, no clinical and radiological signs of disease activity were observed in the annual treatment cycles. NEDA‑3 status was maintained in 37.26% of patients after two years and in 14.94% of patients after five years of treatment. The lack of oligoclonal bands in the cerebrospinal fluid proved to be a favorable prognostic factor affecting the prolongation of the duration of NEDA‑3 status in the treated patients. Conclusions. The maintenance of NEDA‑3 status in patients treated with the first line drugs for over 3 years of therapy is rare.