Participants enrolled in the Optic Neuritis Treatment Trial have been observed for more than a decade to assess the relationship between optic neuritis and the development of clinically definite multiple sclerosis. To assess neurologic disability 10 to 12 years after an initial episode of optic neuritis. Longitudinal follow-up of a clinical trial. Fourteen Optic Neuritis Treatment Trial clinical centers performed standardized neurologic examinations, including an assessment of neurologic disability. One hundred twenty-seven patients who had developed clinically definite multiple sclerosis. Functional Systems Scale and Expanded Disability Status Scale. The disability of most patients was mild, with 65% of patients having an Expanded Disability Status Scale score lower than 3.0. The degree of disability appeared to be unrelated to whether the baseline magnetic resonance imaging scan was lesion-free or showed lesions (P =.51). Among patients with baseline lesions, the degree of disability was unrelated to the number of lesions that were present on the scan (P =.14). Two patients died owing to severe multiple sclerosis, one of whom had no lesions revealed on the baseline scan. Most patients who develop clinically definite multiple sclerosis following an initial episode of optic neuritis will have a relatively benign course for at least 10 years.