OBJECTIVES:Australian aviation medical certification authorities began allowing use of antidepressant medications by aviation personnel in 1987; a sufficiently long period of time and number of personnel involved to allow a preliminary study. The aim of this study was to identify significant safety-related outcomes, such as aircraft accidents or incidents that may be related to the use of antidepressant medication in pilots and air traffic controllers. METHODS:The study employed a matched cohort of all holders of Australian aviation medical certificates who were prescribed antidepressants during the period 1 January 1993 to 30 June 2004 (n = 481), and a matched comparison group. Outcomes of interest were accidents and incidents. RESULTS:No significant differences between the two groups were found in any of the analyses. There were 18 accidents recorded for the antidepressant group and 15 for the comparison group across the whole period, compared with 5 for cases and 5 for controls during the period while antidepressants were being taken. There were 113 incidents recorded for the antidepressant group compared with 131 controls. A non-significantly higher number of accidents and incidents were recorded among cases in the period prior to commencing antidepressant medication. CONCLUSION:This study found no evidence of adverse safety outcomes arising from permitting individuals to operate as commercial or private aircrew or air traffic controllers while using antidepressants provided specific criteria are met and maintained. This finding has the potential to change current policies of aviation regulatory bodies internationally and may be of significance to a range of transport and other safety-critical occupations and activities.