OBJECTIVES: Seizure control through antiepileptic drugs (AEDs) is integral to treatment of Lennox-Gastaut syndrome (LGS). Although six AEDs are approved for LGS (clobazam most recently, October 2011), no standard treatment paradigm has been established. Understanding the economic burden associated with LGS is critical to developing such guidance. The objective of this study was to examine health care resource utilization and costs for patients with LGS. METHODS: Medical and pharmacy claims data (1/1/2007–9/30/2010) from a large US managed health care plan affiliated with OptumInsight were analyzed. Study patients were those with evidence of LGS based on 2 medical claims (≥30 days apart) with diagnosis (ICD-9-CM) of generalized, nonconvulsive (or convulsive) epilepsy. Evidence of developmental diagnoses and 12 months of continuous health plan enrollment following initial epilepsy diagnosis were required. Health care resource utilization and costs were examined during a 12-month follow-up period and computed separately as all-cause, epilepsy-related (i.e., any epilepsy care), or related to seizure-attributable events (e.g., lacerations, fractures). RESULTS: A total of 1,948 patients with evidence of LGS were identified; demographics were consistent with published surveys. Mean counts of epilepsy-related health care visits at 12 months were 10.73 (all-cause: 33.97) for ambulatory visits and 0.75 (all-cause: 0.86) for inpatient admissions. Mean epilepsy-related health care cost was $29,911 (all-cause: $44,797), of which the greatest components were inpatient costs (epilepsy-related: $18,119; all-cause: $19,590) and ambulatory costs (epilepsy-related: $5,515; all-cause: $11,907). Mean medical cost related to seizure-attributable events was $13,038. CONCLUSIONS: A high economic burden was observed in this LGS sample, with frequent health care visits and high costs attributable to epilepsy care. Nearly one-third of total medical costs were associated with seizure-attributable events, highlighting the need for effective seizure control. These results will be useful for understanding the budgetary impact and cost effectiveness of AED therapy in LGS treatment.