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Virtual reality (VR) has gained increased implementation in higher education with reported benefits of enhancing student learning and engagement. However, there is a lack of qualitative research devoted to understanding the prolonged use of VR, and the social process of how instructor’s and students’ behavior and perception toward VR develop and evolve. This research conducted an ethnographic case study of a semester-long VR-integrated neuroanatomy course. By triangulating data from classroom observation, student focus group, and faculty interview, the research results suggested that instructional design of VR was heavily influenced by the instructor’s personal and educational backgrounds, and their technology self-efficacy. The quality of instruction affected students’ perceived value of VR activities and dictated their lived experience in the VR-integrated course.