Background: Photodynamic therapy is a nonthermal laser used for obstructive, bloody lesions in the airway. Methods: A retrospective cohort study of a prospective database was conducted. All patients underwent rigid and flexible bronchoscopy under general anesthesia using jet ventilation. Results: There were 529 operations performed on 133 patients between January 1996 and December 2008. The mean preoperative Modified Medical Research Council Dyspnea Scale grade was 3 of 4. Indications for intervention were non-small cell lung cancer in 89 patients, metastatic airway lesions in 31 patients, small cell disease in 4 patients, benign disease in 7 patients, other or unknown in 2 patients. Tumors were most commonly located in the main stem bronchi (71 patients). A 2.5-cm diffuser was used in 87% of patients, and 300 J (range, 50 to 300 J) was most frequently selected at first treatment. Most patients received two treatments during a 3-day hospitalization and returned in 2 weeks for two more photodynamic therapy treatments. The mean postoperative Modified Medical Research Council Dyspnea Scale grade was 2.7 of 4 and improved in 94 patients (74%). There were 12 operative mortalities (none treatment related). Morbidity occurred in 20 patients (reintubation in 4 patients and respiratory distress leading to an emergent evacuation of debris in 2 patients). Only 4 patients had a photosensitivity reaction. Conclusions: Photodynamic therapy is a safe and effective treatment. It is best used for bloody tumors that block the tracheobronchial tree, even in severely debilitated patients with profound shortness of breath from advanced malignancy who fail conventional core-out or laser treatments. Photosensitivity reactions are rare with proper education, and dyspnea is improved in properly selected patients. © 2010 The Society of Thoracic Surgeons.