Background: Newly acquired long-term cognitive impairments are common among survivors of critical illness. They have been linked to the stressful situation that patients experience in the intensive care unit (ICU). In this paper we use virtual reality (VR) technology to comfort critically ill patients and reduce stress during their ICU stay. We investigate the acceptance, comfort, recollection, and visual perception of VR stimulation and how it affects physiological parameters.Methods: A VR head-mounted display was used to present immersive nature scenes to 33 critically ill cardiac surgery patients [mean age 63 years (range 32-83)]. Data was collected with an eye tracker fitted inside the VR head-mounted display to measure eye movements (250 Hz) and sensors to record physiological parameters (240 Hz). Patients received VR stimulation (for 5 min.) prior to ICU admission, during ICU stay, and 3 months after discharge. Acceptance, recollection and comfort were assessed with validated questionnaires.Results: The number of gazed meaningful objects per minute was significantly lower during the ICU session compared to pre- and follow-up sessions, whereas mean duration of fixation on meaningful moving objects did not differ between the sessions. While respiratory rate decreased significantly during VR stimulation, heart rate and blood pressure remained constant. Post-ICU rating of VR acceptance during ICU stay was moderate to high and discomfort low. Recollection of VR was high [28/33 patients (84.8%)], while recollection of ICU stay was low [10/33 patients (30.3%)].Conclusion: Eye movements indicate that patients were able to perceive and process cognitive stimulation during their ICU stay. VR was recalled better than the rest of the ICU stay and well accepted. Decreased respiratory rate during stimulation indicate a relaxing effect of VR.