Nine patients undergoing video-assisted thoracoscopic surgical (VATS) lung biopsy over a five-year period from 1997 to 2001 with the ultimate diagnosis of usual interstitial pneumonia without underlying connective tissue disease were identified. In two of nine patients, acute exacerbation occurred six days after VATS lung biopsy. We reviewed the clinical records and pathology of all nine cases, and found that the two cases of exacerbation had higher peripheral white blood cell counts and KL-6, lower PaO2, VC and FEV 1, and a longer inhalation of FIO 2 = 1.0 during VATS, and needed a longer period of chest drainage after VATS. Abundant inflammatory cell infiltration and fibroblastic foci were observed in the exacerbation cases. Thus, patients with usual interstitial pneumonia of the idiopathic type, who have high disease activity and low pulmonary function, may be at high risk of acute exacerbation following VATS lung surgery.