This review of migraine prevention is presented in two parallel reports, one focusing on children and one on adults. Here we address migraine prevention in children 6 to 18 years old. According to the International Classification of Headache Disorders, second edition (ICHDII), migraine is a common disabling primary headache disorder manifesting in attacks that last from 4 to 72 hours. Migraine headaches range from moderate to very severe and are sometimes debilitating. Migraine frequency is classified as either episodic or chronic according to the number of monthly migraine days, with episodic being less than 15 days, and chronic being 15 days or more. Migraine may also be described as chronic when attacks recur over long periods of time. Chronic migraine affects 2 % of children and adolescents. Migraine treatments aim either to ameliorate acute attacks or prevent attacks. Many children with frequent or severe migraine need preventive treatment. Our review focuses on preventive treatments for childhood migraine. The Food and Drug Administration has approved no drugs for migraine prevention in children; therefore, pediatricians prescribe drugs approved for adults or off-label drugs (approved for clinical conditions other than migraine prevention). The off-label drug classes that were used cause common and serious adverse effects, including metabolic and hormonal abnormalities. Preventive pharmacologic treatments for migraine in children should be based on the efficacy and safety of the drugs, whether approved for adults or used off label. Preventive treatment aims to eliminate headache pain. Often, however, some pain persists; therefore, treatment success is usually defined by a decrease in migraine frequency of 50 % or more after 3 months. In addition to pain relief, preventive drugs can decrease severity of migraine attacks and reduce restrictions in daily activities and schooling. Our review focuses on the comparative effectiveness and safety of drugs (approved for use in the United States) for preventing migraine attacks in children seen in ambulatory care settings. Our results may help inform treatment recommendations. Key questions addressed include: KQ1: What are the efficacy and comparative effectiveness of pharmacologic treatments for preventing migraine attacks in children? a. How do preventive pharmacologic treatments affect patient-centered and intermediate outcomes when compared with placebo or no active treatment? b. How do preventive pharmacologic treatments affect patient-centered and intermediate outcomes when compared with active pharmacologic treatments? c. How do preventive pharmacologic treatments affect patient-centered and intermediate outcomes when compared with active nonpharmacologic treatments? d. How do preventive pharmacologic treatments combined with nondrug treatments affect patient-centered and intermediate outcomes when compared with pharmacologic treatments alone? e. How might dosing regimens or duration of treatments influence the effects of the treatments on patient-centered outcomes? How might approaches to drug management (such as patient-care teams, integrated care, coordinated care, patient education, drug surveillance, or interactive drug monitoring) influence results? KQ2: What are the comparative harms from pharmacologic treatments for preventing migraine attacks in children? a. What are the harms from preventive pharmacologic treatments when compared with placebo or no active treatment? b. What are the harms from preventive pharmacologic treatments when compared with active pharmacologic treatments? c. How might approaches to drug management (such as patient-care teams, integrated care, coordinated care, patient education, drug surveillance, or interactive drug monitoring) improve safety of the treatments? KQ3: Which characteristics of children predict the effectiveness and safety of pharmacologic treatments for preventing migraine attacks?