We retrospectively reviewed the clinical and radiographic findings in patients with pneumatosis intestinalis (PI), who were identified among 441 patients with cystic fibrosis. Since 1944, the age at onset and the incidence of PI have increased. Pneumomediastinum, pneumothorax, or pulmonary interstitial emphysema was found in 95% of patients with PI compared with 62% of patients without PI. The type, distribution, and severity of PI often changed with time. PI is correlated with the development of obstructive pulmonary disease, which facilitates air dissection into interstitial spaces. Dissection of air is often clinically silent and tends to be self-perpetuating.