AbstractPurposeThe purpose of this study was to develop and preliminarily test a radiotherapy system for patient posture correction and alignment using mixed reality (MixR) visualization. The write‐up of this work also provides an opportunity to introduce the concepts and technology of MixR for a medical physics audience who may be unfamiliar with the topic.MethodsA MixR application was developed for on optical‐see‐through head‐mounted display (HoloLens 2) allowing a user to simultaneously and directly view a patient and a reference hologram derived from their simulation CT scan. The hologram provides a visual reference for the exact posture needed during treatment and is initialized in relation to the origin of a radiotherapy device using marker‐based tracking. The system further provides marker‐less tracking that allows the user tofreely navigate the room as they view and align the patient from various angles. The system was preliminarily tested using both a rigid (pelvis) and nonrigid (female mannequin) anthropomorphic phantom. Each phantom was aligned via hologram and accuracy quantified using CBCT and CT.ResultsA fully realized system was developed. Rigid registration accuracy was on the order of 3.0 ± 1.5 mm based on the performance of three users repeating alignment five times each. The lateral direction showed the most variability among users and was associated with the largest off‐sets (approximately 2.0 mm). For nonrigid alignment, the MixR setup outperformed a setup based on three‐point alignment and setup photos, the latter of which showed a difference in arm position of 2 cm and a torso roll of 6–7°.ConclusionsMixR visualization is a rapidly emerging domain that has the potential to significantly impact the field of medicine. The current application is an illustration of this and highlights the advantages of MixR for patient setup in radiation oncology. The key feature of the system is the way in which it transforms nonrigid registration into rigid registration by providing an efficient, portable, and cost‐effective mechanism for reproducing patient posture without the use of ionizing radiation. Preliminary estimates of registration accuracy indicate clinical viability and form the foundation for further development and clinical testing.