Investigative procedures were approved by Henry Ford Human Investigation Committee and NASA Johnson Space Center Committee for Protection of Human Subjects. Informed consent was obtained. Authors evaluated ability of nonphysician crewmember to obtain diagnostic-quality musculoskeletal ultrasonographic (US) data of the shoulder by following a just-in-time training algorithm and using real-time remote guidance aboard the International Space Station (ISS). ISS Expedition-9 crewmembers attended a 2.5-hour didactic and hands-on US training session 4 months before launch. Aboard the ISS, they completed a 1-hour computer-based Onboard Proficiency Enhancement program 7 days before examination. Crewmembers did not receive specific training in shoulder anatomy or shoulder US techniques. Evaluation of astronaut shoulder integrity was done by using a Human Research Facility US system. Crew used special positioning techniques for subject and operator to facilitate US in microgravity environment. Common anatomic reference points aided initial probe placement. Real-time US video of shoulder was transmitted to remote experienced sonologists in Telescience Center at Johnson Space Center. Probe manipulation and equipment adjustments were guided with verbal commands from remote sonologists to astronaut operators to complete rotator cuff evaluation. Comprehensive US of crewmember's shoulder included transverse and longitudinal images of biceps and supraspinatus tendons and articular cartilage surface. Total examination time required to guide astronaut operator to acquire necessary images was approximately 15 minutes. Multiple arm and probe positions were used to acquire dynamic video images that were of excellent quality to allow evaluation of shoulder integrity. Postsession download and analysis of high-fidelity US images collected onboard demonstrated additional anatomic detail that could be used to exclude subtle injury. Musculoskeletal US can be performed in space by minimally trained operators by using remote guidance. This technique can be used to evaluate shoulder integrity in symptomatic crewmembers after strenuous extravehicular activities or to monitor microgravity-associated changes in musculoskeletal anatomy. Just-in-time training, combined with remote experienced physician guidance, may provide a useful approach to complex medical tasks performed by nonexperienced personnel in a variety of remote settings, including current and future space programs.