Background: Virtual reality (VR) is an evolving technology that is becoming a common treatment for pain management and psychological phobias. While non-immersive devices (i.e., the Nintendo Wii) have been previously tested with hemodialysis patients, no studies to date have used fully-immersive VR as a tool for intervention delivery. The current pilot trial tests the initial safety, acceptability, and utility of VR during maintenance hemodialysis treatment sessions-particularly, whether VR triggers motion sickness that mimics or negatively impact treatment related symptoms (e.g., nausea). Methods: Hemodialysis patients (n=20) were enrolled in a Phase I single-arm proof-of-concept trial. While undergoing hemodialysis, participants were exposed to our new JovialityTM VR program. This 25-minute program delivers mindfulness training and guided meditation using the Oculus Rift head-mounted display. Participants experienced the program on two separate occasions. Prior and immediately following exposure, participants recorded motion-related symptoms and related discomfort on the Simulator Sickness Questionnaire. Utility measures included end-user's ability to be fully immersed in the virtual space, interact with virtual objects, find hardware user-friendly, and easily navigate the JovialityTM program with the System Usability Score scale. Results: Mean age was 55.3 (+/-13.1) years; 80% male; 60% African American; and mean dialysis vintage was 3.56 (+/-3.75) years. At the first session, there were significant decreases in treatment and/or motion-related symptoms following VR exposure (22.6 vs. 11.2; p=0.03); scores >20 indicate problematic immersion. HD end-users reported high levels of immersion in the VR environment and rated the software easy to operate, with average System Usability Scores of 82.8/100. Conclusions: Hemodialysis patients routinely suffer from fatigue, nausea, lightheadedness, and headaches that often manifest during their dialysis sessions. Our JovialityTM VR program decreased symptom severity without adverse effects. VR programs may be a safe platform to improve the dialysis patient experience.