INTRODUCTION: The advancement of human spaceflight has made urgent the need to develop medical imaging technology to ensure a high level of in-flight care. To date, only ultrasound has been used in spaceflight. Radiography has multiple advantages over ultrasound, including lower operator dependence, more rapid acquisition, typically higher spatial resolution, and characterization of tissue with acoustic impedance precluding ultrasound. This proof-of-concept work demonstrates for the first time the feasibility of performing human radiographs in microgravity.METHODS: Radiographs of a phantom and human subject’s hand, knee, chest, cervical spine, and pelvis were obtained aboard a parabolic flight in microgravity and simulated lunar gravity with various subject and operator positions. Control radiographs were acquired with the same system on the ground. These radiographs were performed with a Food and Drug Administration-approved ultra-portable, wireless, battery-powered, digital x-ray system.RESULTS: The radiographs of the phantom acquired in reduced gravity were qualitatively and quantitatively compared to the ground controls and found to exhibit similar diagnostic adequacy. There was no statistically significant difference in contrast resolution or spatial resolution with a spatial resolution across all imaging environments up to the Nyquist frequency of 3.6 line-pairs/mm and an average contrast-to-noise ratio of 2.44.DISCUSSION: As mass, power, and volume limitations lessen over the coming decades and the miniaturization of imaging equipment continues, in-flight implementation of nonsonographic modalities will become practical. Given the demonstrated ease of use and satisfactory image quality, portable radiography is ready to be the new frontier of space medical imaging.Lerner D, Pohlen M, Wang A, Walter J, Cairnie M, Gifford S. X-ray imaging in the simulated microgravity environment of parabolic flight. Aerosp Med Hum Perform. 2023; 94(10):786–791.