| Summary: | (1) Background: The use of virtual reality (VR) in improving patient comfort related to medical procedures in oncology patients raised the question of whether similar benefits could be obtained by patients with inflammatory bowel disease (IBD). (2) Methods: In this prospective, randomized, controlled, single-center clinical trial, a total of 90 patients with IBD treated with vedolizumab were enrolled and randomized in a 1:1 allocation to either the VR immersion group or the routine-treated group. The primary outcome was to evaluate whether VR could decrease stress and anxiety related to a medical procedure. The secondary outcome was to assess the safety of the VR. (3) Results: A statistically significant improvement in well-being and psychological comfort (<i>p</i> = 0.046), feeling of relaxation (<i>p</i> = 0.046), sense of influence on the treatment process (<i>p</i> < 0.001), improved perception of the way the drug works (<i>p</i> < 0.001), improved positive attitude while waiting for the next administration of the drug (<i>p</i> = 0.026), and increased motivation for treatment (<i>p</i> = 0.026) was noticed in the intervention group. There were no statistically significant differences in the incidence of complications in the intervention and control groups. (4) Conclusions: The use of VR had a positive effect on the reduction of stress associated with vedolizumab treatment and could improve compliance.
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