Virtual Reality (VR) is a simulation technique that utilizes computer-generated environments, allowing for the creation of controlled, reproducible, and standardized settings. The main benefit of VR lies in its ability to produce a sense of presence, enabling users to engage in the learning process as though they were experiencing the events in real life. These benefits can be extended to specialized training such as cardiopulmonary resuscitation (CPR). VR is highly effective for CPR education, offering an immersive, interactive, and multi-sensory experience that enhances realism compared to traditional methods. Although VR offers significant potential for teaching basic life support and early defibrillation (BLSD), it does have limitations: users are unable to experience the physical resistance. This randomized controlled study describes the development of the VR BLSD scenario at phase 6 of the Research and Development cycle: main field testing. This study aims to determine whether a VR-based BLSD scenario, can closely mimic the experience of a traditional BLSD training course. The trial was conducted in one nursing school in Rome (Italy), on a convenience sample of third-year nursing students. This pilot study confirmed that the VR BLSD scenario, was acceptable, and usability and level of presence experienced were good. Although satisfaction and self-confidence scores were slightly lower in the VR group, the differences were not statistically significant, indicating that VR-based training may serve as a viable complementary approach in BLSD education. Furthermore, large-scale trials should be conducted to evaluate the effectiveness of the VR BLSD scenario, compared to traditional BLSD scenario, and the impact on participants’ learning outcomes.