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This study aimed to evaluate methylphenidate-associated body mass index (BMI) changes and treatment discontinuation across weight status groups in children and adolescents, using real-world data. We used data from the BMI Epidemiology Study (BEST) Gothenburg cohort linked to the Swedish National Prescribed Drug Register. We included children (< 18 years) initiating methylphenidate, with BMI measurements available at baseline and one year. A subgroup also had BMI measurements at two years. We analysed changes in standardized BMI (zBMI) by baseline weight status and evaluated the impact of dosing and drug discontinuation. Methylphenidate treatment was associated with significant zBMI reduction across all weight status groups in the first treatment year, with the largest decrease observed in those with obesity (-0.5 SD, p = 0.01). Higher dose increases, younger age, and female sex were associated with larger zBMI reductions. During the first year, obesity prevalence decreased from 10.4% to 5.7% (p < 0.001), while underweight increased from 6.6% to 13.1% (p < 0.001). Individuals with underweight or normal weight had higher odds of discontinuation, compared with those with overweight or obesity (OR = 1.73, p = 0.004). In the second year, zBMI and weight status remained largely stable. In conclusion, in this real-world setting, methylphenidate was associated with BMI reductions across all weight status groups during the first treatment year. The greatest reduction was seen in individuals with obesity. For those continuing treatment the second year, BMI remained stable.