Incapacitation of a pilot due to the effects of a medical condition or a physiological impairment represents a serious potential threat to flight safety. The purpose of this research project was to investigate the prevalence, type, nature and significance of in-flight medical conditions and incapacitation events occurring in civil aviation. A search of the Australian Transport Safety Bureau's accident and incident database was conducted for medical conditions and incapacitation events between 1 January 1975 and 31 March 2006. There were 98 occurrences in which the pilot of the aircraft was incapacitated for medical or physiological reasons (16 accidents, one serious incident and 81 incidents). Such events accounted for only 0.6 of a percentage point of all the occurrences listed in the Australian Transport Safety Bureau's database. The majority of the events occurred in airline operations, with private flying the next most common (22.4 per cent of events). In 10 occurrences (10.2 per cent), the outcome of the event was a fatal accident. All of these accidents involved single-pilot operations, and in the majority of cases, heart attack was the most common cause. The majority (21 per cent) of in-flight medical and incapacitation events in Australian civil pilots for the study period were due to acute gastrointestinal illness (usually food poisoning), a finding consistent with other published studies. The next most common cause was exposure to toxic smoke and fumes on board the aircraft, of which 25 per cent were due to carbon monoxide. The results of this study demonstrate that the risk of a pilot suffering from an in-flight medical condition or incapacitation event is low. However, if the pilot suffers a heart attack the risk of a fatal accident occurring increases. The aeromedical certification process must keep pace with the evolving nature of modern medical science to ensure that the risk of in-flight incapacitation remains low.