BACKGROUND: Although optic neuritis (ON) is common in multiple sclerosis (MS), lesions of the optic nerve are not included as an anatomical substrate for dissemination in space and time (DIS and DIT). OBJECTIVE: To assess the increase in sensitivity of including MRI lesions of the optic nerve for the diagnosis of MS in patients with ON. METHODS: We included patients consecutively referred with first time, monosymptomatic ON, with no known cause of the ON, who underwent orbital MRI including fat suppressed T2 and T1-sequences with and without gadolinium contrast. RESULTS: One hundred and twenty patients were included. Optic nerve T2 lesions and/or T1-contrast enhancement was shown in 104 patients. Sixty-three patients were diagnosed with MS at baseline. Nine patients developed MS during follow-up. The inclusion of optic nerve MRI lesions led to the diagnosis of 8 additional patients and increased sensitivity to 0.99 (95% CI 0.96-1.00) compared to 0.88 (95% CI 0.79-0.95) for 2017 criteria, while decreasing the specificity to 0.81 (95% CI 0.70-0.92) compared to 1.00. CONCLUSION: Amending the diagnostic criteria for MS to include MRI lesions of the optic nerve as a substrate for DIS and DIT may increase sensitivity and lead to more rapid diagnosis of MS.