INTRODUCTION: Accessible spaceflight may seem a distant concept. As part of a diverse European Space Agency funded Topical Team, we are working on the physiological feasibility of space missions being undertaken by people with physical disabilities. Here, the first activity of this team is presented in the form of key lessons learned from aviation to inform new work on space missions.DISCUSSION: The first lesson is agreeing on realistic expectations about impairments, their severity, and the possibility of flying independently. This is important in terms of astronaut recruitment and societal expectations. The second lesson relates to training and adjustments for people with disabilities. Flexibility is important while maintaining safety for everyone involved. The third lesson is about managing unconscious bias from the different stakeholders. We conclude by arguing that engagement with people from different backgrounds is essential for the success of the first space mission with people with physical disabilities.Miller-Smith MJ, Tucker N, Anderton R, Caplin N, Harridge SDR, Hodkinson P, Narici MV, Pollock RD, Possnig C, Rittweger J, Smith TG, Di Giulio I. Lessons for flying astronauts with disabilities drawn from experience in aviation. Aerosp Med Hum Perform. 2024; 95(9):716-719.