Abstract Background Different non-pharmacological techniques, including hypnosis and virtual reality (VR) are currently used as complementary tools in the treatment of anxiety, acute and chronic pain. A new technique called virtual reality hypnosis (VRH), which encompasses a combination of both tools, is regularly used although its benefits and underlying mechanisms remain unknown to date. With the goal to improve our understanding of VRH combination effects, it is necessary to conduct randomised and controlled research trials in order to understand their clinical interest and potential benefits. Methods Patients (n = 100) undergoing cardiac surgery at the Liège University Hospital will be randomly assigned to one of four conditions (control, hypnosis, VR or VRH). Each patient will receive two sessions of one of the techniques: one the day before the surgery and one the day after. Physiological assessments will be made on the monitor and patients will rate their levels of anxiety, fatigue, pain, absorption and dissociation. Discussion This study will help to expand knowledge on the application of virtual reality, hypnosis and VRH in the specific context of cardiac and intensive care procedures, and the influence of these non-pharmacological techniques on patient’s anxiety, fatigue, pain and phenomenological experience. Trial registration ClinicalTrials.gov: NCT03820700. Date registered on 29 January 2019. Study recruitment date: October 6, 2018. Study anticipated completion date: December 28, 2020.