BACKGROUND: Alveolar-pleural fistula with persistent air leak is a common problem causing significant morbidity, prolonged hospital stay, and increased health-care costs. When conventional therapy fails, an alternative to prolonged chest-tube drainage or surgery is needed. New bronchoscopic techniques have been developed to close the air leak by reducing the flow of air through the leak. The objective of this study was to analyze our experience with bronchoscopic application of a synthetic hydrogel for the treatment of such fistulas. METHODS: We conducted a retrospective study of patients with alveolar-pleural fistula with persistent air leaks treated with synthetic hydrogel application via flexible bronchoscopy. Patient characteristics, underlying disease, and outcome of endoscopic treatment were analyzed. RESULTS: Between January 2009 and December 2013, 22 patients (14 men, eight women; mean age ± SD, 62 ± 10 years) were treated with one to three applications of a synthetic hydrogel per patient. The primary etiology of persistent air leak was necrotizing pneumonia (n = 8), post-thoracic surgery (n = 6), bullous emphysema (n = 5), idiopathic interstitial pneumonia (n = 2), and sarcoidosis (n = 1). Nineteen patients (86%) had complete resolution of the air leak, leading to successful removal of chest tube a mean (± SD) of 4.3 ± 0.9 days after last bronchoscopic application. The procedure was very well tolerated, with two patients coughing up the hydrogel and one having hypoxemia requiring bronchoscopic suctioning. CONCLUSIONS: Bronchoscopic administration of a synthetic hydrogel is an effective, nonsurgical, minimally invasive intervention for patients with persistent pulmonary air leaks secondary to alveolar-pleural fistula.