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The responses of different patients to the same drug may vary as a consequence of biologic, psychosocial, and genetic differences. The aim of this study was to identify clinical factors associated with a response to pharmacologic treatment in pediatric patients with migraine.The medical files of patients with migraine attending the headache clinic of a tertiary pediatric medical center in 2010-2015 were reviewed. The children and parents (or only the parents if the child was very young) completed the International Headache Society-based questionnaire. Patients were treated with at least one of the following medications: propranolol, amitriptyline, topiramate. Response to treatment was rated as no change in migraine pattern (grade 1) or a decrease in migraine attack frequency per month by at least 50% (grade 2) or at least 75% (grade 3). The highest-grade response to any pharmacologic treatment was defined as the best clinical response.The study group included 248 patients of mean age 12.71 ± 3.04 years. A grade 3 best clinical response was significantly associated with a positive maternal history of migraine, younger age at treatment onset, lower frequency of headache attacks per month, postpubertal children had a significantly lower rate of grade 3 response than prepubertal children (P< .05). Analysis of the association of overuse of medication and treatment response achieved aPvalue equal to .05.Several background and clinical factors are identified that may predispose children with migraine to respond better to pharmacologic treatment. Clinicians who see children with migraine in a pediatric headache clinic setting should consider these factors before initiating a treatment program.