BACKGROUND In this experimental study, the effectiveness of N-butyl cyanoacrylate tissue adhesive on preventing air leakage after pulmonary wedge resection was observed. METHODS Twenty pairs of sheep lungs were used. Before initiating the study, the sheep lungs were ventilated to identify any air leakage from the parenchyma. On positive results, those sheep lungs were then excluded from the study. Wedge resection was performed on the right and left lower lobes of sheep lungs by clamping the edges forming a triangle of 5 cm × 5 cm × 5 cm. One side of parenchyma was sutured by 3/0 vicryl (Group A) while the other side of parenchyma was sealed by N-butyl cyanoacrylate (Group B). After waiting for 5 min for N-butyl cyanoacrylate to dry, the sheep lungs were intubated by 6F endotracheal tubes. The lungs were soaked in a bath tub filled with 10 cm deep water and inflated by 40 mmHg pressure to record any air leakage from the parenchyma partially sutured by vicryl and sealed by N-butyl cyanoacrylate. RESULTS Air leakages were observed on the parenchyma surfaces of group of lungs (100%) sutured by vicryl (minimal 30%, mild 50% or massive 20% levels), while only on four of (20%) the other group of lungs sealed by N-butyl cyanoacrylate, minimal air leakage was observed on the parenchymal surface. There was an extremely significant difference between Group A and Group B in terms of the development of air leakage (p=000). CONCLUSIONS We consider that, N-butyl cyanoacrylate could be used effectively and safely to prevent air leakage from the pulmonary wedge resection surface.