Objective: Cognitive impairment is a core symptom of pediatric-onset multiple sclerosis (MS), although relatively little is known regarding the rate of cognitive decline. This study examined the extent, pattern, and correlates of change in cognitive functioning in youth with MS. Method: Changes in cognitive performance in 28 patients with pediatric-onset MS and 26 age-matched controls were ascertained through repeat comprehensive neuropsychological assessment conducted over a 1-year period. Change was evaluated by using a mixed factorial design with repeated measures to determine the interaction between group and time and using the Reliable Change Index (RCI) to determine individual differences on test scores over time. Participants were classified as showing “decline” or “improvement” if change scores exceeded the RCI on three or more tests. Results: The pattern of change over time differed by group. At the group level, healthy controls were more likely to show improvement across multiple domains of function relative to the MS group. Using the RCI, 7 of 28 patients (25%) showed cognitive deterioration compared with only 1 of 26 controls (3.8%; p < .05). Performance on measures of attention and processing speed, visuomotor integration, verbal fluency, visual memory, and calculation and spelling ability were most responsive to deterioration in functioning over time. Longer disease duration was associated with greater deterioration in visuomotor integration. Increased lesion volume was associated with slower psychomotor speed over time. Conclusion: Lower rates of improvement in the pediatric MS group may be suggestive of a lack of age-appropriate cognitive development and warrant further evaluation over time.