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Background: Port-a-catheter (PAC) placement is a common procedure in oncology that, despite local anaesthesia, can induce patient discomfort, procedural pain, and anxiety. Virtual reality hypnosis (VRH), combining immersive virtual reality with clinical hypnosis, has been proposed as a non-pharmacological adjunct to reduce peri-procedural distress. Objectives: This pilot study aimed to explore the suitability of VRH during PAC placement and its potential effects on pain, anxiety, and VRH-related experiences, while investigating psychological variables associated with VRH engagement. Methods: In this single-arm interventional monocentric prospective pilot study, twenty oncology patients undergoing first-time elective PAC placement received a VRH intervention delivered via a medical-grade head-mounted display throughout the procedure. Pain, anxiety, and VRH-related dimensions—including absorption, dissociation, automaticity, arousal, and sense of presence—were assessed pre- and post-procedure using self-reported numerical rating scales and questionnaires. Non-parametric Wilcoxon tests evaluated pre–post changes, and correlational analyses (Pearson’s and Spearman’s when necessary) explored associations between variables. Results: VRH was well tolerated by most participants, although three patients required additional pharmacological support, and four could not complete the session due to intolerance or technical issues. Anxiety scores decreased significantly following VRH, whereas pain showed a non-significant trend toward reduction. Post-procedural absorption and dissociation were positively associated with presence, and higher absorption traits were linked to greater immersive engagement and prior VR/hypnosis experience. Cybersickness was negatively associated with absorption. Older age was correlated with lower post-procedural pain, and females reported higher state anxiety. Conclusions: In this pilot, VRH was feasible, well tolerated, and associated with a significant exploratory reduction in procedural state anxiety. Given the single-arm design, these findings constitute directional evidence warranting controlled trial evaluation rather than proof of efficacy. These preliminary results support the rationale for randomised controlled trials to evaluate VRH efficacy, underlying mechanisms, and potential role as a non-pharmacological adjunct in oncology perioperative care.