AIMS: Malignant mesothelioma is increasing in incidence and no current therapy significantly prolongs survival. Previous surgical strategies involved high-risk open procedures without achieving histologically clear resection margins. We present the results of VATS debulking pleurectomy-decortication in advanced disease. METHODS: A consecutive series of patients with suspected malignant mesothelioma underwent thoracoscopic assessment to determine the feasibility of decortication, where this was not possible a biopsy alone was taken. Post-operative radiotherapy was administered to port sites, but no other adjuvant therapy was given. The two groups (biopsy only and pleurectomy-decortication) were composed of patients with histologically confirmed mesothelioma [28 and 51 patients, respectively]. The primary endpoint was comparison of actuarial patient survival. Secondary endpoints included post-operative air leak and duration of hospital stay. RESULTS: The overall actuarial survival was 288 days and 67% of patients had died at the time of data analysis. The groups were matched for patient and tumour-related characteristics including age (66, 64 years, p=0.39) and tumour stage (median IMIG stage 3 [IQR 2-3] both groups, p=0.54). The biopsy only group had fewer air leaks (57, 84%, p=0.01) and a shorter hospital stay (4, 8 days, p=0.03). However, the pleurectomy-decortication group had favourable actuarial survival relative to the biopsy only group (416, 127 days, p<0.001). Multivariate analysis showed early stage (p<0.001), absence of pre-operative fever (p=0.03) and pleurectomy-decortication (p<0.001) as independent predictors of survival. CONCLUSION: VATS pleurectomy-decortication is feasible in the majority of cases and independently improves survival for patients with advanced malignant mesothelioma.