OBJECTIVES: Choosing an antiepileptic drug (AED) can be a complex decision for clinicians. This study aims to estimate the cost-effectiveness of levetiracetam adjunctive therapy compared to topiramate adjunctive therapy for the treatment of refractory primary generalised tonic-clonic seizures (PGTCS) in the Scottish health care setting. METHODS: A Markov model was developed to assess the clinical and economic outcomes of levetiracetam adjunctive therapy compared to topiramate adjunctive therapy in patients with refractory PGTCS. The model simulates the treatment pathway of a hypothetical cohort of 1000 patients over one year. Efficacy data were drawn from five randomized clinical trials. Data for each three-month cycle on risk of withdrawal, adverse events and mortality were obtained from the published literature. Resource use data and costs were obtained from published data and were based on the Scottish NHS perspective. Only direct costs relating to the management and treatment of refractory PGTCS and adverse events were considered. Health benefits were assessed in terms of seizure-free cycles and quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses explored the robustness of the results. RESULTS: In the base case scenario, the model predicts approximately 3800 seizure-free cycles for topiramate versus 4000 for levetiracetam. QALYs gained are slightly higher for levetiracetam than topiramate (990 vs. 980). Total costs relating to topiramate and levetiracetam are similar (£1,555,000 and £1,500,000 respectively). Consequently, levetiracetam adjunctive therapy dominates topiramate adjunctive therapy. Varying AED costs did not have a major impact on the results of the cost-effectiveness analysis. Using a threshold of £30,000 per QALY, levetiracetam is cost-effective compared to topiramate in 85% of refractory PGTCS patients. CONCLUSION: Levetiracetam adjunctive therapy appears to be cost-effective for the treatment of refractory patients with PGTCS. Levetiracetam adjunctive therapy dominates topiramate adjunctive therapy, its acquisition cost being offset by reduced seizure management costs and a better tolerability profile.