ImportanceOptimizing ADHD stimulant therapy in children is difficult due to individual variability and lack of reliable response predictors, forcing a trial-and-error approach that burdens both patients and families.ObjectiveTo identify factors associated with treatment success based on real-world patterns of ADHD stimulant use.DesignSetting and participants: In this retrospective cohort study we used the comprehensive electronic health records of Maccabi Healthcare Services. We included children aged 6–18 years diagnosed with ADHD between 2015–2023 who had purchased at least one ADHD stimulant and had at least 1 year of follow-up. Patients were classified as persistent users once they purchased at least eight prescriptions over a fixed 12-month period, with each purchase covering a 30-day period, and there were no gaps of 90 days or more; others were defined as non-persistent. Data was stratified by stimulant type using the WHO Anatomical Therapeutic Chemical classification. Demographic and clinical covariates were analyzed to identify factors associated with sustained medication use. The study followed the STROBE Statement.ResultsThe cohort comprised of 43,825 children with ADHD, of which 18,783 (43%) were Persistent users. Persistent users were more often of male sex (67.5% vs. 55.4%), lower socioeconomic status (44.7% vs. 42.4% with low or very low SES), and initiated treatment at a younger age (76.4% vs. 52.9% initiated treatment at 6–12 years). Lisdexamfetamine was associated with the highest odds of treatment persistence when used as the initial stimulant, compared with the reference group (OR = 2.2, CI = 1.86–2.59), although this finding was based on a relatively small sample (n = 654).Conclusion and RelevanceIn this retrospective cohort study of pediatric patients with ADHD, male sex, low socioeconomic status, early treatment initiation, and first-line lisdexamfetamine were associated with higher persistence.