Australia has conducted expeditions to the Antarctic for more than a century. The Australian Antarctic Division (AAD) has maintained a permanent presence in East Antarctica since 1954, now with three Antarctic research stations (Casey, Davis and Mawson) and one sub-Antarctic research station on Macquarie Island. Each station is supported by an Antarctic Medical Practitioner who is responsible for the comprehensive medical, surgical, anaesthetic and dental care of their expeditionary team with advanced training and telehealth support provided by the Polar Medicine Unit in Tasmania. The Polar Medicine Unit has had an operational and research collaboration with the National Aeronautics and Space Administration (NASA) since 1993 which has facilitated scientific and operational studies examining human risks associated with spaceflight. In 2023, the AAD entered into an agreement with the Translational Research Institute for Space Health (TRISH) of the Baylor College of Medicine, providing access to Australia’s Antarctic space analogue environment for research that will support the health of Antarctic expeditioners and astronaut crews undertaking long duration exploration missions. Astronauts on these missions will experience increased physical isolation and will require greater autonomy as spaceflight extends further from Earth. This will require new approaches to crew selection, medical training, resourcing and clinical support which have not been required in low earth orbit. The AAD’s long history of operating established Antarctic research stations over isolated Antarctic winters and the advanced medical capabilities provided by the Polar Medicine Unit provide a medical model well suited to future long duration spaceflight.