Background <p>Transvaginal ultrasound-guided oocyte retrieval (TVOR) is a critical and essential step in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for the treatment of infertility. However, it is generally considered an uncomfortable and painful procedure. Recent studies have demonstrated the effectiveness of virtual reality (VR) in reducing pain intensity in various acute pain scenarios, including procedural pain. This study aims to evaluate the efficacy and safety of VR interventions in alleviating pain and anxiety among women undergoing TVOR.</p> Methods <p>A parallel-group, prospective randomized controlled trial (RCT) was conducted at the Center for Reproductive Medicine of Chongqing Health Center for Women and Children between 1 June 2022 and 30 July 2023. A total of 113 women who underwent TVOR were randomly assigned to either the VR group (<i>n</i> = 55) or the control group (<i>n</i> = 58), with all participants successfully completing the study. In the VR group, patients wore VR devices to simulate the experience of oocyte retrieval on the preoperative day and watched VR videos during the procedure. The control group received only standard care. The primary outcomes were changes in pain and anxiety scores. The secondary outcomes included changes in physiological parameters, adverse effects, operation cooperation, and pregnancy outcomes in both groups.</p> Results <p>Pain scores were significantly lower in the VR group than in the control group both during the procedure (median, interquartile range [IQR]: 3 [2–4] vs. 4 [2–5], <i>p</i> &lt; 0.001) and 1 h postoperatively (median [IQR]: 2 [1–3] vs. 3 [2–4], <i>p</i> &lt; 0.05). Preoperative anxiety levels measured 10 min before the procedure were also lower in the VR group (mean, standard deviation [SD]: 37.45 [4.92] vs. 39.89 [5.34]; 95% CI: -4.355 to -0.520, <i>p</i> &lt; 0.05). Intraoperative physiological monitoring revealed a reduced mean heart rate (mean [SD]: 85.38 [0.87] vs. 90.62 [13.08]; 95% CI: -0.144 to 3.666, <i>p</i> &lt; 0.05) and respiratory rate (mean [SD]: 15.64 [2.70] vs. 19.04 [11.40]; 95% CI: 0.168 to 6.422, <i>p</i> &lt; 0.05) in the VR group compared with the control group. No significant between-group differences were observed in adverse effects or pregnancy rates (<i>p</i> &gt; 0.05 for all comparisons).</p> Conclusion <p>This RCT demonstrated that VR significantly reduced pain and anxiety compared with standard care during TVOR, offering a safe, feasible nonpharmacologic adjunct that may reduce opioid needs and shorten the clinic turnover time. These findings provide evidence for integrating VR into routine ART workflows as an alternative, patient-centred intervention, although future multicentre, large-sample studies are needed to evaluate long-term efficacy across diverse clinical settings.</p> Trial registration <p>The study was registered in the Chinese Clinical Trial Registry with the code ChiCTR2200060212 on 22/5/2022.</p>