Objectives This study aimed to determine anthropometric and clinical correlates of persistence to methylphenidate (MPH) treatment in Turkish youth with attention-deficit hyperactivity disorder (ADHD). Methods Data from medical records of 518 children and adolescents with ADHD were recorded between March 2012 and January 2022. Clinical variables of patients persistent to MPH ≥ 2 years were compared with those of the non-persistent group. Children and adolescent age groups were compared using Kaplan–Meier estimates for treatment drop-outs. Cox regression analysis until the treatment drop-out was implemented to calculate hazard ratios (HRs) for gender, age, full-scale IQ, and anthropometric measures. Weight, height, and body mass index (BMI) z-scores were calculated per national guidelines. Results Persistent and non-persistent study groups had similar full-scale IQ, weight, height, and BMI z-scores at treatment onset. The mean MPH dose was significantly higher in the persistent group compared to the non-persistent counterparts (31.43 ± 10.70 vs. 24.28 ± 9.60 mg/d, p < 0.001, d = 0.70). Compared to children, the adolescents showed earlier treatment drop-outs in males (p < 0.001) but not in females (p = 0.110). Younger age showed a positive effect on treatment persistence. Conversely, baseline BMI and IQ scores were not associated with long-term persistence. Discussion Our study demonstrated lower daily doses and older age-onset were associated with early drop-outs in MPH treatment. These findings supported the notion that effective dosing strategies at younger ages could increase the sustainability of the treatment with MPH in the Turkish population.