Due to increasing demands in the content that needs to be covered in physiology and anatomy, as well as the increased need to dedicate time to clinical skills practice, medical students can benefit from the introduction of effective tools to enhance their level of engagement with learning material while promoting knowledge retention. One of the key aspects of medical education is mastering the terminology, science and clinical application of human anatomy, which some students may perceive as challenging in their pre-clinical years (1). However, there are substantial limitations for students to effectively learn anatomy due to the restrictions regarding the time frame in which they have face-to-face access to a cadaver. Students studying the human body from illustrations or textbooks may find it challenging to understand the complex interactions of organs in 3D space (2). A new disruptive technology, mixed reality through the use of holograms, has been introduced as a tool which can render the human body in a full 3D environment (3). The aim of this study was to investigate and compare the effectiveness of holographic technologies using Microsoft’s HoloLens against an identical lesson on a tablet-based augmented reality platform, to assess students’ perceptions, experiences, and knowledge acquisition. Thirty-eight participants were randomly allocated to either mixed reality (HoloLens) or augmented reality (AR) group to complete a lesson of the structure and function of the brain. Participants completed a five-question pre-test before the lesson, as well as a post-test questionnaire consisting of 10 questions evaluating the acquired knowledge of the structure and function of the brain discussed in the lesson. After the lesson, participants completed two Likert-style questionnaires evaluating the adverse health effects experienced and the participant engagement with the learning module. A Mann-Whitney U test was undertaken to analyze pre- and post-test scores, as well as the significance between the adverse health effects experienced and enjoyability using the learning tools. At baseline, there was no significant difference in knowledge between the two groups. The average post-test scores for the AR group was 74% and for the HoloLens group was 79%, with no significant differences between knowledge gained. Both augmented reality and holograms resulted in similar adverse health effects experienced during the lesson, however the participants in the holograms group experienced a significant increase in the severity of dizziness. The holograms group rated a higher overall enjoyment with their learning tool and reported a significantly higher rating towards the clearness of instructions and labels in the brain lesson compared to the AR group. Finding ways to improve and optimize learning for the diverse range of learners in today’s higher education classrooms can be challenging. Variations in the disruptive technology devices, the introduction of mixed reality, and other new modes provide a range of options for educators wishing to adopt technology-enhanced learning within their curricula (4). This study provided evidence that the HoloLens is as effective as AR-based lessons for learning and engagement within physiology education.