BACKGROUND: Virtual reality (VR) helps control symptoms during procedures in chronic patients. This study analyzes VR's effect on pain and anxiety in hemodialysis (HD) patients at two points: the vascular access puncture and disconnection. METHODS: A prospective, non-randomized, crossover, multicenter pilot study assessing pre- and post-intervention outcomes with VR headsets. The intervention group used VR for up to 13 sessions, around the puncture, and at the end of the session. Pain was measured with the Faces Pain Scale - Revised (FPS-R) and anxiety with the Visual Analogue Scale for Anxiety (VAS-A). Usability and patient satisfaction with VR were also evaluated. RESULTS: A total of 73 patients (66.2 ± 13.3 years, 67% men) were included. At the start, 8.2% declined to wear the VR headset. The average number of sessions with the headset was 6.5 ± 4.8, with 23.3% completing all 13 sessions. Pain during punctures significantly improved with VR (1.26 vs 0.97; p = 0.039), while anxiety improved non-significantly. Anxiety during disconnection slightly increased, but also not significantly. Patients with higher initial pain and anxiety levels during puncture and disconnection showed significant improvement, while those with lower initial levels worsened (p < 0.05 in all cases). The HD population showed varying levels of acceptance of VR. CONCLUSION: VR headsets help reduce pain during punctures, especially in patients with more intense pain. The effect on anxiety reduction during punctures or at the end of the session is inconclusive, with better results in those with higher anxiety levels. VR acceptance in the HD population is variable.