Background: Optic neuritis (ON) is one of the earliest manifestations of multiple sclerosis (MS). The prevalence of bilateral ON (BON) as the presenting symptom is not clear. The aim of this study was to evaluate the prevalence of BON as the presenting symptom in MS and compare it with unilateral ON (UON). Subjects and Methods: In this study, two groups of definite MS patients according to the McDonald's criteria were enrolled: Thirty patients with BON and fifty persons with UON (selected randomly from all of the UON patients) as the presenting manifestation. The patients' data were collected from the Isfahan MS Society Registry. The SPSS 22 software was used for analysis of the data. P Results: Thirty of 3972 MS patients presented with BON. The mean of their ages was 26.00 ± 6.29 in BON and 30.10 ± 8.25 in UON group ( P = 0.015). Twenty-five of BON patients were females, and five were males and in the UON group, 42 were females, and eight were males. Expanded disability status scale was 1.83 ± 1.17 in BON and 1.84 ± 1.25 in UON group ( P = 0.975). The severities of relative afferent pupillary defect (RAPD) (in pluses) were 2.00 ± 0.52 and 1.43 ± 0.72 in two groups, respectively. Conclusions: The prevalence of BON as the presenting symptom was about 0.7%. The patients who presented with BON were younger at the time of diagnosis when they were compared with those who diagnosed with UON and also had a more severe RAPD. BON could be considered as one of the important presenting manifestations of MS.