INTRODUCTION: Commercial air travel is usually without health incidents. However, there is a view that cabin environments may be detrimental to health, especially flights of 8 h or more. Concerns have been raised about deep vein thrombosis, upper respiratory tract infections, altitude sickness, and toxins from the engines.METHODS: Passenger cabin simulators were used to achieve a comparative observational study with 8-h flights at pressures equivalent to terrestrial altitudes of ground, 4000, 6000, and 8000 ft. Biomarkers of thrombosis (D-Dimer), inflammation (interleukin-6), and respiratory dysfunction (FEV₁) and oxygen saturation (S_po₂) were measured, as well as pulse and blood pressure. The wellbeing of the passengers was also monitored.RESULTS: During 36 flights, 1260 healthy subjects [626 women (F) and 634 men (M) (mean age = 43, SD = 16)] were assessed. Additionally, 72 subjects with chronic obstructive pulmonary disease (F = 32, M = 40, mean age = 48, SD = 17) and 74 with heart failure (F = 50, M = 24, mean age = 54, SD = 14) contributed to 11 flights. Additionally, 76 normal controls were observed while engaged in a usual day’s work (F = 38, M = 38, mean age = 39, SD = 15). There were no health-significant changes in D-Dimer, interleukin-6, or FEV₁. S_po₂ varied as expected, with lowest values at 8000 ft and in patients with cardiopulmonary disease. The only differences from the controls were the loss of the normal diurnal variations in interleukin-6 and D-Dimer.DISCUSSION: This very large, comparative, controlled study provides much reassurance for the traveling public, who use airline flights of up to 8 h. We did not show evidence of the development of venous thrombosis, inflammation, respiratory embarrassment, nor passenger distress. No significant symptoms or adverse effects were reported.Ideal Cabin Environment (ICE) Research Consortium of the European Community 6^th Framework Programme. Health effects of airline cabin environments in simulated 8-hour flights. Aerosp Med Hum Perform. 2017; 88(7):651–656.