OBJECTIVES: Lennox-Gastaut syndrome (LGS) is a debilitating form of epilepsy characterized by developmental disorders and high frequency of drop attacks that are often refractory to antiepileptic drug (AED) therapy. Clobazam was approved by the FDA in October 2011 for adjunctive treatment of seizures associated with LGS. We developed a model to compare the budget impact of adding clobazam to an AED portfolio containing topiramate, lamotrigine, and rufinamide in a hypothetical 100,000-member health care plan. METHODS: Patient characteristics and AED efficacy (decrease from baseline in frequency of drop seizures) were modeled with clinical trial data. Medical costs were derived from administrative claims data from a large US managed health care plan affiliated with OptumInsight, with the assumption that 2.3% of drop seizures required medical care. Budget impact was measured over 2 years. Results were expressed as overall difference in costs (seizure and pharmacy) to a health plan, and cost per member per month (PMPM) after the addition of clobazam. Alternative scenario analyses were performed. RESULTS: With the assumption that 0.04 % of the plan population had LGS, addition of clobazam to the formulary resulted in cost savings of $78,600 in Year 1 and $104,000 in Year 2, corresponding to savings of $0.07 and $0.09 PMPM, respectively. Alternative analyses with lower seizure rates upon discontinuation or greater long-term efficacy for lamotrigine and topiramate did not substantially alter the conclusion. Assumption that fewer drop seizures require medical care resulted in a modest cost increase with clobazam, suggesting that medically attended drop seizures are a primary driver of costs for LGS patients. CONCLUSIONS: Medically attended drop seizures are a major cost driver for LGS patients. Our results demonstrate that adding clobazam to a health care plan formulary can have a positive overall budget impact through a decrease in medical costs associated with drop seizures.