OBJECTIVES: To evaluate the relative likelihood of severe cutaneous reactions (Steven-Johnson Syndrome, toxic epidermal necrolysis), aseptic meningitis, and organ dysfunction (pancreatitis, hepatotoxicity) associated with antiepileptic drugs (AEDS) in children (aged 2-18 years) as compared to adults (aged 19+) with epilepsy. METHODS: This retrospective cohort study analyzed patients in a large nationally representative administrative claims database between 2006 and 2011. The sample consisted of Medicaid, Medicare, and Commercial patients with a diagnosis of epilepsy (ICD-9-CM 345.X) who were continuously enrolled with pharmacy benefits for 6-months and had no prior AEDS fills (new users).  Multivariate analysis (logistic regression) was used to follow eligible patients from index date to first adverse event or up to six months after AED initiation. RESULTS: The study population included 1,803,871 new users of AEDS. Children comprised 7.9% (N=142,874, female=50.7%, age=12.4 [± 4.7]) and adults 92.1% (N=1,660,997, female=64.6%, age=52.8 [± 17.7]).  Compared to adults, children were significantly less likely to experience organ dysfunction (OR=0.228, 95% CI: 0.20-0.26, p<0.0001), but more likely to have severe cutaneous reactions (OR=1.19, 95% CI: 1.14-1.25, p<0.0001) after controlling for potential confounders (gender, region, type of medication).  There was no significant age effect on risk of aseptic meningitis.  Female adults had a statistically lower likelihood of organ dysfunction compared to males (OR=0.75, 95% CI: 0.72-0.77, p<0.0001), but there was no gender effect for risk of organ dysfunction in children.  Females in both groups had a higher likelihood of developing cutaneous reactions compared to males (adults: OR=1.28, 95% CI: 1.25-1.31, p<0.0001; children: OR=1.20, 95% CI: 1.15-1.26, p<0.0001). CONCLUSIONS: Adverse effects resulting from treatment with AEDS are an important consideration in evaluating epilepsy treatment options.  This study provides new information about the comparative risks of AEDS that can be used to guide optimal prescribing practices for patients with epilepsy.