Mesothelioma incidence in the United Kingdom is predicted to increase rapidly from 1300 cases per annum to an estimated 3000 cases by 2020. Mesothelioma is invariably fatal with a median survival of 9 months following diagnosis. Despite its rising importance as a cause of cancer mortality there is a deficit of evidence-based therapeutic options for mesothelioma. The majority of patients (up to 80%) have dyspnoea and a unilateral pleural effusion at the time of presentation. Currently, there is no consensus as to the best method to control pleural effusion in this condition. In many centres, the most rapid and logistically feasible approach is talc pleurodesis via an intercostal chest drain or by ‘medical’ thoracoscopy. However, this is not always successful and subsequent surgery is sometimes necessary. The aim of this study is to compare the effectiveness and cost effectiveness of video-assisted thoracoscopic (VAT) cytoreductive pleurectomy against talc pleurodesis for patients with pleural effusion secondary to mesothelioma.