Background <p>Clinical and epidemiological studies have reported a comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and migraine. Pharmacological treatments such as methylphenidate have also been hypothesized to contribute to the onset of headaches. This study aimed to investigate the percentage of headaches in a pediatric ADHD population, comparing children treated with methylphenidate to those not receiving pharmacological therapy, while also considering the potential influence of family history, sex, and age.</p> Methods <p>A retrospective cross-sectional analysis was conducted on 118 children and adolescents diagnosed with ADHD (68 treated with methylphenidate, 50 untreated). Headache presence and features were assessed using a structured questionnaire based on international diagnostic criteria. Binomial and multinomial logistic regressions were used to evaluate the effects of methylphenidate use and family history on headache presence and type, controlling for age and sex.</p> Results <p>Headache symptoms were significantly more frequent in participants with a family history of headache, regardless of medication status. No main effect of methylphenidate on overall headache percentage was observed. However, the combination of methylphenidate treatment and positive family history was significantly associated with migraine-compatible headache presentations. Cephalalgy was not significantly linked to any of the variables. The absence of family history was strongly associated with the absence of headache symptoms.</p> Conclusions <p>Family history appears to be a key factor in headache percentage among children with ADHD. While methylphenidate alone does not increase headache risk, its interaction with familial predisposition may contribute to migraine-like symptoms. Family history should be carefully considered during clinical assessment.</p>