The surgical arm of trimodality therapy for malignant pleural mesothelioma includes two principal procedures used for cytoreduction, namely, extrapleural pneumonectomy and pleurectomy and decortication. The more radical of the two procedures, extrapleural pneumonectomy, can be performed with acceptable morbility and mortality at experienced centers. This article provides a detailed description of the operation followed by a discussion of the clinical results and complications observed during our 12-year experience at the Brigham and Women's Hospital Thoracic Surgery Division and Dana Farber Thoracic Oncology Program.