BACKGROUND: Whether the unique environment of space affects astronaut risk of venous thromboembolism (VTE) is not known. On Earth, it is known that use of combined oral contraceptives (COCs) doubles the risk of VTE. Since some female astronauts choose to use COCs, this retrospective study examined known risk factors associated with VTE risk to determine whether the available data suggested elevated VTE risk in female astronauts.METHODS: Longitudinal health data were requested for female astronauts who flew short and long duration missions between 2000 and 2014. Pre- and postflight hematological and biochemical blood markers were available and evaluated. Astronauts' postflight measurements were compared to clinically relevant terrestrial high risk levels to determine any trend toward increased risk for VTE following spaceflight. Secondarily, a comparison of pre- and postflight changes was made, as well as an assessment of COC impact.RESULTS: A total of 38 astronaut-flights were included in this study and no VTE events were found. Analysis of potential VTE risk factors showed no evidence suggesting elevated VTE risk in female astronauts associated with spaceflight, regardless of contraceptive use.DISCUSSION: Arguably, all astronauts encounter many physiological stressors during spaceflight missions, but women using the combined contraceptive pill add a known risk factor for VTE. The risk factors analyzed within this study showed no trend toward an increased risk of VTE for female astronauts. This study provides an evidence base supporting the safety of COC use by female astronauts and also reinforces the importance of healthy lifestyle on VTE risk reduction.Jain V, Ploutz-Snyder R, Young M, Charvat JM, Wotring VE. Potential venous thromboembolism risk in female astronauts. Aerosp Med Hum Perform. 2020; 91(5):432-439.