Background <p>Emerging evidence implies a link between high pediatric body mass index (BMI) and an increased risk of multiple sclerosis (MS). However, previous research suggests this association is only present for adolescent obesity and not childhood obesity. The present study aimed to assess the association between pediatric obesity and risk of developing MS, and to investigate if degree of obesity and age at obesity treatment initiation affects the risk. In a subgroup, response to obesity treatment on MS risk was assessed.</p> Methods <p>In this cohort study, patients aged 2–19 years from the Swedish Childhood Obesity Treatment Register (BORIS), and matched individuals from the general population were followed prospectively. MS was identified through the National Patient Register. Hazard ratios (HR) adjusted for parental MS were calculated.</p> Results <p>The study included 21,652 individuals with pediatric obesity and 102,187 general population comparators. The median age at follow-up was 21 (Q1, Q3 18, 25) years. The adjusted HR (95% CI) for developing MS in the pediatric obesity cohort was 2.28 (1.45–3.58). In stratified analyses, obesity class I was not associated with MS, HR = 1.34 (0.64–2.81), while the association between obesity class II and MS was strengthened, HR = 3.42 (1.89–6.19). MS was associated with both childhood obesity, HR = 3.16 (1.12–8.87), and adolescent obesity, HR = 2.12 (1.28–3.51). A decrease in BMI SDS was not associated with lower likelihood of MS, HR = 1.09 (0.92–1.29) per 0.25 BMI SDS unit decrease.</p> Conclusions <p>Both childhood and adolescent obesity are associated with an increased risk of MS. Moreover, a dose-response relationship between the degree of obesity and the risk of future MS was indicated, while response to pediatric obesity treatment did not affect the association, highlighting the importance of preventing high degree of obesity early in life.</p>