Background: The objective of this study was to assess the safety of general thoracic surgery in patients taking antiplatelet (clopidogrel) therapy. Methods: A prospective study was conducted of consecutive patients who underwent general thoracic surgery and who were taking clopidogrel perioperatively. They were matched using a propensity score from our prospective database of 11,768 patients. Intraoperative and postoperative outcomes were compared. Results: Between January 2009 and April 2010 there were 33 patients on clopidogrel at the time of surgery and 132 controls. The most common procedures were thoracotomy with lobectomy in 11 patients (robotic in 1), video-assisted wedge resection in 6, mediastinoscopy in 4, and Ivor Lewis esophagogastrectomy in 2. Epidurals were not used. There was no intraoperative morbidity or bleeding in primary thoracotomy; however, 2 of the 4 patients who underwent redo thoracotomy had bleeding that required transfusions. None of the 8 patients receiving clopidogrel who had a coronary artery stent and underwent lobectomy had a perioperative myocardial infarction whereas 5 of the 14 control patients undergoing lobectomy who had a coronary artery stent did (P = .05). Otherwise, morbidity, mortality, and length of stay were no different. Conclusions: Patients who are receiving clopidogrel and who have a coronary artery stent placed can safely undergo general thoracic surgery. The widely held belief that surgery cannot be performed without bleeding is untrue. This new finding not only eliminates much of the preoperative dilemma posed by these patients but also may reduce their risk of a postoperative myocardial infarction. However, patients who require a redo thoracotomy may be at increased risk of bleeding. © 2010 by The American Association for Thoracic Surgery.