Commercial aircraft flight represents a highly variable altitude exposure that may result in significant hypoxemia for patients with cardiac or pulmonary disease. To develop better guidelines for travel by patients with cardiopulmonary disease, we measured inflight cabin altitude on 204 regularly scheduled commercial aircraft flights. Measurements were carried out on 16 different types of aircraft, operated by 28 airlines. The median altitude exposure for all flights was 6,214 feet (1894 m). Cabin altitudes ranged from sea level to 8,915 feet (2717 m). Inspired partial pressure of oxygen falls from 159 mm Hg at sea level to 127 mm Hg at 6,200 feet and further declines to 113 mm Hg at 9,000 ft. There was no significant difference between domestic and international flights. New generation aircraft fly at higher altitudes than older aircraft and are associated with greater altitude exposures to passengers (p = 0.002). The risk of hypoxemia may increase as newer model aircraft replace older ones.