OBJECTIVES: Compared to adults relatively little is known about drug safety in children. This study aims to describe the drugs and adverse events most commonly reported in the US spontaneous Adverse Event Reporting System (AERS) in children. METHODS: Adverse events reported to the US FDA AERS Database between 1 January 2007 and 30 June 2012 and occurring in children and adolescent (<18 years old) were examined. Demographic characteristics of the patients and reports were described by age, gender and reporter type. Additionally, the most commonly suspected drugs and the most frequently occurring adverse events in the AERS database were identified.  RESULTS: We identified a total of 90,355 reports (average 16,428 reports/year) of primary suspect medications in children, of which 60.8% were for individuals < 12 years old and 50.6% were males. Physicians (30.5%) and consumers (27.4%) reported the majority of pediatric adverse drug events. Methylphenidate was the most frequently reported drug with 3,755 (4.2%) reports, followed by infliximab (3.0%) and isotretinoin (2.7%). Vomiting (1.3%), pyrexia (1.2%), convulsion (1.1%), drug ineffective (1.0%) and product quality issue (0.9%) were the top five reported adverse events. However, dyspnoea and pneumonia became the fourth and fifth leading adverse events respectively when restricting our analysis to only severe events (i.e., resulting in hospitalization, life-threatening events, or death). CONCLUSIONS: Data from post-marketing surveillance of adverse events can add to our understanding of drug safety in children.  A large proportion of events reported to the FDA are not considered severe and focusing solely on severe events is likely important to identify potential high risk medications.  Subsequent analyses of the most commonly reported drug causes of severe adverse events may lead to important safety questions.