Background This study evaluated the clinical significance of perioperative levels of plasma blood coagulation factor XlII in patients undergoing pulmonary resection. Methods The study involved 27 patients with ≥2day prolonged air leakage after pulmonary resection. The 27 pulmonary resection procedures comprised 25 lobectomies, 1 segmentectomy, and 1 partial resection. The preoperative and 5-day postoperative blood coagulation factor XIII levels were measured. Results Perioperative changes in the blood coagulation factor XlII levels showed no significant correlation with the preoperative hemoglobin Aic levels. The mean postoperative blood coagulation factor XIII level was 78.2±15.7% in patients with postoperative total protein levels of <6.6 g/dL, and 102.1±19.7% in patients with postoperative total protein levels of ≥6.6 g/dL (p=0.018). The mean drainage duration was 8.3 ±2.7 days in patients with postoperative blood coagulation factor XIII levels of ≤70% and 5.3 2.3 days in patients with levels of >70% (p=0.017). Conclusions Low blood coagulation factor XIII levels may be associated with prolonged air leakage and thereby exogenous blood coagulation factor XIII may lead to shorter drain placement durations in patients undergoing thoracic surgery, particularly patients with a poor nutritional status.