Secondary pneumothorax is caused by underlying chest diseases such as pulmonary emphysema and interstitial pneumonia. There has been little comparative study of these two diseases and combined pulmonary fibrosis and emphysema (CPFE) complicated by pneumothorax. We retrospectively investigated 48 hospitalized cases of secondary pneumothorax occurring in patients with these three etiologies. Significantly more interstitial pneumonia patients and CPFE patients were low BMI and receiving long-term oxygen therapy than did pulmonary emphysema patients, moreover, these two factors were significant poor prognostic factors. Compared with the pulmonary emphysema group, the median survival time for patients with interstitial pneumonia (non-CPFE) was only 6.2 months, while in comparison with the CPFE group, there was no significant difference. The fact that in patients with interstitial pneumonia (non-CPFE) a low BMI and receiving long-term oxygen therapy can constitute a high risk for pneumothorax and an unfavorable prognosis should be recognized.