Training medical professionals for hand hygiene is challenging, especially due to the invisibility of microorganisms to the human eye. As the use of virtual reality (VR) in medical training is still novel, this exploratory study investigated how preexisting technology acceptance and in-training engagement predict VR hand hygiene performance scores. The effect of training in the VR environment on the behavioral intention to further use this type of training device (a component of technology acceptance) was also investigated. Participants completed a VR hand hygiene training comprising three levels of the same task with increasing difficulty. We measured technology acceptance, composed of performance expectancy, effort expectancy, and behavioral intention, pre- and post-training, and in-training engagement using adaptations of existing questionnaires. We used linear regression models to determine predictors of performance in level-3 and of behavioral intention to further use VR training. Forty-three medical students participated in this exploratory study. In-training performance significantly increased between level-1 and level-3. Performance in level-3 was predicted by prior performance expectancy and engagement during the training session. Intention to further use VR to learn medical procedures was predicted by both prior effort expectancy and engagement. Our results provide clarification on the relationship between VR training, engagement, and technology acceptance. Future research should assess the long-term effectiveness of hand hygiene VR training and the transferability of VR training to actual patient care in natural settings. A more complete VR training could also be developed, with additional levels including more increased difficulty and additional medical tasks.