OBJECTIVES: To assess the cost-effectiveness of using a lidocaine 5% medicated plaster in the treatment of post-herpetic neuralgia (PHN) compared with gabapentin and pregabalin from the perspective of the payer in Spain. METHODS: A Markov model was constructed to calculate the cost-effectiveness of gabapentin, pregabalin and lidocaine plaster in terms of the cost per quality-adjusted life-year (QALY) gained when used over a six-month time horizon in patients with PHN. The model structure allowed for differences in costs, utilities and transition probabilities between the initial 30-day run-in period and maintenance therapy. Transition probabilities were based on the comparative and long-term clinical trials identified through a systematic literature review. Missing data, including resource utilization, were obtained from a Delphi panel, and cost data were obtained from the official price/tariffs lists. Utilities were derived from the literature and were supplemented and validated by the Delphi panel. RESULTS: The total cost of treatment with the lidocaine plaster was €1414 per patient at a daily consumption of 1.1 plasters, compared with €1100 for gabapentin (average dosage 2100 mg/day during maintenance phase), and €1348 for pregabalin (average dosage 488 mg during maintenance phase). Lidocaine plaster generated 0.428 QALYs, compared with 0.339 for gabapentin, and 0.399 for pregabalin. Lidocaine plaster therefore had an incremental cost-effectiveness ratio of €3525/QALY gained relative to gabapentin at generic price, and €742/QALY relative to pregabalin. Scenario analyses and extensive one-way sensitivity analyses on all parameters including the time horizon confirmed the robustness of the results. CONCLUSIONS: The lidocaine 5% plaster is a highly cost-effective treatment for PHN in Spain.