The use of cardiopulmonary bypass (CPB) for locally advanced thoracic malignancies is highly controversial. The purpose of this study was to document the techniques and results of CPB to facilitate the resection of complex thoracic malignancies and to identify common themes that provided for successful outcomes. This was a retrospective study that took place from January 1992 to September 2002. Fourteen consecutive patients (median age, 59 years; age range, 18 to 69 years; seven men and seven women) underwent CPB during the resection of locally advanced thoracic malignancies at two Boston hospitals. CPB was planned in 8 of 14 patients (57%) with centrally located tumors, while 6 of 14 patients (43%) required emergent institution of CPB due to injury of the superior vena cava (2 patients), inferior vena cava (2 patients), or pulmonary artery (2 patients). Complete microscopic resection was achieved in 12 of 14 patients (86%). The operative mortality rate was 1 of 14 patients (7%) due to pulmonary embolism (ie, the elective group). The median ICU and hospital lengths of stay were 5 and 9 days, respectively. The overall 1-year, 3-year, and 5-year survival rates were 57%, 36%, and 21%, respectively. The planned use of CPB to facilitate complete resection of thoracic malignancies should be considered only after careful patient selection. The availability of CPB also provides a safety net in the event of injury to vascular structures during tumor resection.