OBJECTIVE:To determine the value-for-money offered by pemetrexed (Alimta) plus cisplatin therapy for patients with malignant pleural mesothelioma (MPM), relative to cisplatin monotherapy, in Australia. MPM is an uncommon, locally invasive and rapidly fatal malignancy. There is currently no other drug reimbursed by the Australian National Formulary specifically for the treatment of mesothelioma. METHODS: A comprehensive literature search revealed one randomised head-to-head trial of pemetrexed plus cisplatin therapy versus cisplatin monotherapy (N = 448) by Vogelzang et al. (2003). Median survival for the intention-to-treat (ITT) population was 12.1 months for the pemetrexed plus cisplatin arm versus 9.3 months for the cisplatin arm (hazard ratio = 0.77, p = 0.020). Although there was greater toxicity with the combination regimen, quality of life was not negatively impacted. Mean survival time for each treatment arm was estimated from Kaplan-Meier survival curves. Resource use was applied as per the trial and costed accordingly. Study drug utilisation, concomitant medications, supplementary medication (dexamethasone, folic acid, and vitamin B12), post-study chemotherapy, and care for serious and treatment-emergent adverse events were costed. RESULTS: Patients received a mean of 4.7 treatment cycles in the pemetrexed plus cisplatin arm, and 4.0 cycles in the cisplatin monotherapy arm. The combination therapy required more supportive care for toxicities. The additional mean cost of pemetrexed plus cisplatin therapy, over cisplatin monotherapy, was A$14,032.78 per patient. The mean and median survival gain with pemetrexed plus cisplatin therapy was found to be 0.191 and 0.233 years, respectively, relative to cisplatin monotherapy, over the 27-month period of observation. The cost per life-year saved was A$73,470.04 for mean and A$60,226.52 for median incremental survival. CONCLUSIONS: This survival benefit is a highly patient-relevant outcome. This economic evaluation found that pemetrexed plus cisplatin therapy offers an acceptable cost-effectiveness ratio for a small population of MPM patients in Australia.