We sought to evaluate the efficacy and safety of a synthetic bioresorbable pleural sealant (PleuraSeal; Covidien, Bedford, Mass) to treat air leaks after pulmonary resection. METHODS: Patients with air leaks after lung resection were randomized to treatment with pleural sealant on air leak sites after standard methods of lung closure or standard lung closure only. The primary outcome variable was the percentage of patients remaining air leak free until discharge. The secondary outcome variables were the proportion of patients with successful intraoperative air leak sealing, time to last air leak, and durations of chest tube drainage and hospitalization. RESULTS: The sealant group comprised 62 subjects, and the control group comprised 59 subjects. Most patients (98.3 ) underwent open lobectomy for bronchogenic carcinoma. The overall success rates for intraoperative air leak sealing were as follows: sealant group, 71.0 ; control group, 23.7 (P <.001). For grade 2 and 3 air leaks (n = 77), the intraoperative sealing rates were as follows: sealant group, 71.7 ; control group, 9.1 (P <.001). More patients with grade 2 and 3 air leaks had their leaks remain sealed in the sealant group (43.5 vs 15.2 , P = .013). The median time from skin closure to last observable air leak was 6 hours (sealant group) versus 42 hours (control group, P = .718). No treatment-related complications were reported. No differences in drainage or hospitalization were observed.