AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.