This research investigates the effectiveness of virtual reality (VR) for enhancing neuroanatomy learning among medical students, focusing on optimizing cognitive load, intrinsic motivation, and user experience. Conducted with 77 second-year medical students, the study compares traditional video-based instruction with three VR inter- action conditions: active, guided, and passive. VR significantly improved anatomical learning performance compared to traditional methods, particularly in the passive and active conditions. Specifically, VR enhanced intrinsic motivation, optimized cognitive load by reducing extraneous load, and improved germane load. Additionally, the guided VR condition yielded the poorest learning performance, though it did not significantly differ from the other two VR conditions, suggesting that interactivity is not the primary factor driving VR’s effectiveness. The findings highlight the complex relationship between cognitive load, intrinsic motivation, and learning performance, supporting a balanced approach to using VR for educational purposes. The role of domain expertise and interaction modes within VR are discussed as critical factors in VR’s instructional efficacy.