The HoloLens (Microsoft Corp., Redmond, WA), a head-worn, optically see-through augmented reality display, is the main player in the recent boost in medical augmented reality research. In medical settings, the HoloLens enables the physician to obtain immediate insight into patient information, directly overlaid with their view of the clinical scenario, the medical student to gain a better understanding of complex anatomies or procedures, and even the patient to execute therapeutic tasks with improved, immersive guidance. In this systematic review, we provide a comprehensive overview of the usage of the first-generation HoloLens within the medical domain, from its release in March 2016, until the year of 2021, were attention is shifting towards it’s successor, the HoloLens 2. We identified 171 relevant publications through a systematic search of the PubMed and Scopus databases. We analyze these publications in regard to their intended use case, technical methodology for registration and tracking, data sources, visualization as well as validation and evaluation. We find that, although the feasibility of using the HoloLens in various medical scenarios has been shown, increased efforts in the areas of precision, reliability, usability, workflow and perception are necessary to establish AR in clinical practice.