OBJECTIVES: Prolonged alveolar air leak is the most common complication after pulmonary surgery. We conducted an investigator-led randomized trial to evaluate the effectiveness of CoSeal® surgical sealant (Cohesion Technologies Inc.; manufactured and distributed by Baxter Healthcare) for the closure of alveolar air leak after anatomical pulmonary resection. METHODS: Patients undergoing primary open lobectomy, bilobectomy, or sublobar resection with a demonstrable air leak on intra-operative testing were randomized to either standard care or standard care plus application of CoSeal® surgical sealant to areas of air leak. A second application of CoSeal® was used in the treatment group if air leak persisted. Patients were allocated at the point of entry to the trial by unbiased allocation with minimization to ensure balance between the two arms with respect to age, sex, surgeon, number of segments resected, preoperative forced expiratory volume in 1s (FEV₁), and grade of air leak. Kaplan-Meier analysis of air-leak duration and a log rank test were performed on an intention-to-treat basis, with observations censored at death, transfer to the intensive care unit, or discharge. RESULTS: Of the 200 patients, who entered the trial over a 24-month period, 121 with demonstrable intra-operative air leak were randomly allocated to the two groups. Data were missing for one patient in the CoSeal® group. In 57%, the air leak was stopped at the first application; a quarter continued to leak after the second. At 24h, there was no difference in air leak and fewer patients in the control group were leaking at 48 h postoperatively. By log rank test, the difference was not significant (p=0.09). CONCLUSIONS: Patients treated with CoSeal® in this study had, as a group, a longer duration of air leak and hence we cannot recommend its routine use.