OBJECTIVES: To evaluate the cost-effectiveness of rufinamide relative to topiramate and lamotrigine as adjunctive treatment of Lennox-Gastaut Syndrome (LGS) a severe and devastating form of childhood epilepsy. METHODS: A Markov state transition model was developed with 4 health states WC75, WC50, NC (corresponding to ³75%, ³50% and<75%, and <50% reduction in tonic-atonic (drop attack) seizure frequency respectively) and “death”. Efficacy and safety data were obtained from the literature. Transition probabilities were derived from patient level trial data for rufinamide. In the absence of head to head clinical studies, indirect/mixed treatment comparisons were used to obtain efficacy and safety estimates. LGS related health state utilities were obtained from a utility study which was carried out among the UK general public and caregivers/parents using the time trade off (TTO) method and EQ-5D questionnaires. Treatment benefit, as reflected with percent of patients achieving a given degree of reduction of drop-attack SF over a three year horizon, were translated to quality adjusted life years (QALYs). Medical resource and cost data were obtained from an expert panel survey and published sources. Costs were estimated from the perspective of the UK NHS and personal social services. Probabilistic sensitivity analyses were carried out. Cost and benefits were discounted according to UK guidelines. RESULTS: The primary base-case analysis using TTO utilities found that, over 3 years, rufinamide was associated with an incremental cost per QALY of £20,538 relative to topiramate and £154,831 relative to lamotrigine.  A secondary analysis using EQ5D utilities found that rufinamide was associated with an incremental cost per QALY of £12,034 relative to topiramate and £56,446 relative to lamotrigine. CONCLUSIONS: This study with its underlying assumptions and data demonstrates that rufinamide should be considered as a treatment option for LGS, particularly as treatment choice is important for this rare and devastating condition.