Purpose <p>This study aimed to evaluate the feasibility and analgesic potential of a guided breathing virtual reality (VR) intervention for managing pain in patients with cancer undergoing percutaneous transhepatic biliary drainage (PTBD).</p> Methods <p>In a randomized, controlled design, patients were assigned to receive either VR with guided deep breathing (VRBG) or conventional VR without breath guidance (VROG). Each group experienced two 7-min VR sessions featuring calming visuals and narration, with the VRBG receiving additional prompts to induce slow, rhythmic breathing.</p> Results <p>A total of 45 patients (VRBG, 22; VROG, 23) were enrolled. On the day following PTBD, opioid consumption was significantly lower with VRBG than with VROG (20.25 vs. 56.61 morphine milligram equivalents; <i>P</i> = 0.044). No significant difference was observed in opioid use on the day of the procedure. Patient satisfaction and willingness to reuse VR were comparable between the groups. Mild adverse events were infrequent and self-limiting.</p> Conclusion <p>The study findings suggest that incorporating structured breathing guidance into VR may enhance its analgesic effect and reduce reliance on opioids after invasive procedures. To our knowledge, this is the first prospective trial to combine VR and guided breathing for PTBD-related pain, and our findings support the potential of guided breathing VR as a non-pharmacological adjunct in cancer pain management.</p> <p>Trial Registration</p> <p>Clinical Research Information Service (<a href="http://cris.nih.go.kr">http://cris.nih.go.kr</a>, KCT0006775).</p>