INTRODUCTION: In-flight medical events (IMEs), although rare, are challenging due to the limited onboard resources and the time needed to reach an airport. Cabin crewmembers (CCMs) are trained to provide first aid, but their effectiveness has not been appropriately studied.METHODS: IMEs occurring in the biggest airline of Greece were prospectively recorded during a 5-yr period (20142018) and categorized according to a symptom-based taxonomy.RESULTS: During the study period 990 IMEs were recorded corresponding to 16 IMEs for each million passengers or 1.8 IMEs for every thousand flights. The most frequent events were loss of consciousness (38.4%) followed by injuries (8.6%), gastrointestinal problems (8.3%), respiratory symptoms (7.3%), anxiety (5.7%), and burns (5.9%). Diversion was decided in 3% of the cases while death on board was rare (0.3% of events). CCMs responded in 33.5% of IMEs without assistance by a volunteer health professional, achieving a 97% success rate.DISCUSSION: IMEs are rare events and the majority can be treated with simple first aid measures. CCMs acting according to a simplified algorithm were very efficient in providing first aid. A standardized symptom-based IME form will assist in creating a reliable registry for further studies.Paxinos O, Savourdos P, Alexelis V, Anastasopoulos A, Karantoni E, Grigoropoulos P, Konstantinou X. In-flight medical events and cabin crew first aid response. Aerosp Med Hum Perform. 2021; 92(1):3238.