Objective To undertake a cost-effectiveness evaluation of pemetrexed/cisplatin (pem/cis) compared to cisplatin (cis) for patients with advanced malignant pleural mesothelioma (MPM) in Scotland Method The efficacy of pem/cis versus cis was evaluated in the first randomised phase III trial in patients with unresectable MPM (Vogelzang 2003). Emergent data early in the trial led to patients being fully supplemented with folic acid and vitamin B12. Survival benefit was assessed in fully vitamin-supplemented patients with advanced disease [FS (stage III/IV)]. A cost/life-year saved (LYS) analysis of FS (stage III/IV) cohort using the median survival gain from the clinical trial was undertaken. This cohort was chosen because it represented the most realistic use of pemetrexed in Scottish clinical practice: most MPM patients in Scotland have advanced disease at presentation (Aziz 2002) and vitamin supplementation is mandatory with pemetrexed treatment (ALIMTA SPC). Specific unit costs were applied to drug acquisition, administration, supportive care medication, hospitalisations for serious adverse events and post-study chemotherapy, with incidence derived directly from the clinical trial. A discount rate of 3.5% per annum was applied to all outcomes. Results The survival of pem/cis over cisplatin in this cohort was 13.2 versus 8.4 months (p=0.003; HR 0.63 [95%CI 0.46-0.86]). The incremental per patient cost for pem/cis compared to cis was £8,196. The incremental cost/LYS for this cohort is £20,844 The robustness of the model was tested using one-way sensitivity analyses on key variables affecting both cost and outcomes estimates in the cost-effectiveness model. Little variation in the incremental cost/LYS was found with the variables tested for the FS with advanced disease patients (£17,500 - £25,000). Conclusions The trial demonstrated clear survival gain for the cohort of fully supplemented pem/cis patients with advanced disease. This analysis demonstrates that the combination may be considered a cost-effective treatment for patients with advanced MPM.