Purpose To determine the relationships among age, unilateral versus bilateral simultaneous presentation, magnetic resonance imaging (MRI) lesions, and the risk of multiple sclerosis (MS) in children with optic neuritis. Methods A systematic literature review and meta-analysis were performed by the use of a MEDLINE search to identify published studies containing individual patient data for children with optic neuritis. Age, laterality (unilateral vs bilateral simultaneous optic neuritis), presence of brain MRI abnormalities, and development of MS were recorded. Logistic regression was used to determine the relationships among these parameters. Results Fourteen studies met inclusion criteria. Data for 223 patients (age range 2-17.8 years) were analyzed. Unilateral optic neuritis occurred more frequently in older children but was not associated with an increased risk of MS, after adjusting for age (odds ratio [OR] = 1.9, P = 0.11; 95% confidence interval [CI], 0.9-4.3). For every 1-year increase in age, the odds of developing MS increased by 32% (OR = 1.3, P = 0.005; 95% CI, 1.1-1.6, adjusted for the presence of MRI lesions). The risk of MS was greater in children with abnormal brain MRI scans at presentation compared with normal MRIs (OR = 28.0, P < 0.001, 95% CI, 6.3-125.1, adjusted for age). Conclusions The relationship between unilateral and bilateral optic neuritis and the development of MS is dependent on age. Older children and those with brain MRI abnormalities at presentation, are at greater risk for MS. Long-term follow-up of children with optic neuritis is needed to establish the true risk for the development of MS.