The operating room (OR) is a demanding and high-pressure environment for healthcare professionals. This study aims to use virtual reality (VR) technology to introduce health profession students to the OR environment in a controlled and immersive way. Using a quasi-experimental design with pre-post measures we aim to investigate the effect of a VR OR simulation on students’ anxiety, stress, self-efficacy and knowledge acquisition. We recruited 40 second-year nursing students without prior OR experience and divided them into two groups: one experiencing the OR through a VR display and the other through a slideshow presentation of the same environment. We assessed anxiety, stress, self-efficacy and knowledge level before and after intervention. Results indicated a significant increase in self-efficacy for the two groups. The VR group also showed increase in anxiety in association with decrease in stress levels. Knowledge acquisition improved in both groups. This study underlines VR’s potential as an effective tool for OR familiarization, significantly enhancing self-efficacy and reducing stress among nursing students