OBJECTIVES: To compare costs and health benefits of two therapeutic options for the first line treatment of chemotherapy naïve patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) – gemcitabin/cisplatin versus pemetrexed/cisplatin. METHODS: A lifetime 3-week cycle Markov model was developed and adapted for Portugal in order to estimate costs per life year (LY) and per quality adjusted life year (QALY) gained for patients with adenocarcinoma and large cell carcinoma histology. The model considers three disease states – stable, response, progression – and two treatment phases – during and after first line treatment. Patients may suffer from adverse events such as neutropenia and febrile neutropenia; fatigue; diarrhoea; nausea and vomiting; bleeding; anaemia; and thrombocytopenia. The clinical inputs to the economic model were obtained from phase 3 pivotal trial. Direct medical costs were estimated according to both the Society’s and the NHS perspectives. A Delphi panel was conducted in order to estimate resource consumption. Unit costs were derived from official sources. RESULTS: Patients treated with pemetrexed have a discounted expected LY 1.226 compared to 1.104 of those treated with gemcitabine. Due to the low quality of life of the population considered, QALY are 0.655 and 0.595, respectively. Incremental costs with pemetrexed are below €3,900 for both perspectives due to its higher price and to a larger consumption of best supportive care. Therefore, the incremental cost per LY gained is €31,154 for the Society (€63,859 per QALY) and €30,950€ for the NHS (€63,441€ per QALY). Sensitivity analysis shows that these findings are only affected by the assumptions adopted on the mean body surface area, drug wastage and overall survival. CONCLUSIONS: The incremental cost per LY of pemetrexed is acceptable. However, the incremental cost per QALY is higher than usual thresholds due to the low basal quality of life of the population.