Airlines commonly report respiratory in-flight emergencies; flight outcomes have not been examined prospectively in large numbers of respiratory patients. The current authors conducted a prospective, observational study of flight outcomes in this group. UK respiratory specialists were invited to recruit patients planning air travel. Centres undertook their usual pre-flight assessment. Within 2 weeks of returning, patients completed a questionnaire documenting symptoms, in-flight oxygen use and unscheduled healthcare use. In total, 616 patients were recruited. Of these, 500 (81%) returned questionnaires. The most common diagnoses were airway (54%) and diffuse parenchymal lung disease (23%). In total, 12 patients died, seven before flying and five within 1 month. Pre-flight assessment included oximetry (96%), spirometry (95%), hypoxic challenge (45%) and walk test (10%). Of the patients, 11% did not fly. In those who flew, unscheduled respiratory healthcare use increased from 9% in the 4 weeks prior to travel to 19% in the 4 weeks after travel. However, when compared with self-reported data during the preceding year, medical consultations increased by just 2%. In patients flying after careful respiratory specialist assessment, commercial air travel appears generally safe.