Background The global market for medical education is projected to increase exponentially over the next 5 years. A mode of delivery expected to drive the growth of this market is virtual reality (VR). VR simulates real-world objects, events, locations, and interactions in 3D multimedia sensory environments. It has been used successfully in medical education for surgical training, learning anatomy, and advancing drug discovery. New VR research has been used to simulate role-playing and clinical encounters; however, most of this research has been conducted with health professions students and not current health care professionals. Thus, more research is needed to explore how health care professionals experience VR with role-playing and clinical encounters. Objective The aim of this study was to explore health care professionals’ experiences with a cinematic VR (cine-VR) training program focused on role-playing and clinical encounters addressing social determinants of health, Appalachian culture, and diabetes. Cine-VR leverages 360-degree video with the narrative storytelling of cinema to create an engaging educational experience. Methods We conducted in-depth telephone interviews with health care professionals who participated in the cine-VR training. The interviews were audio recorded and transcribed verbatim. A multidisciplinary team coded and analyzed the data using content and thematic analyses with NVivo software. Results We conducted 24 in-depth interviews with health care professionals (age=45.3, SD 11.3, years; n=16, 67%, women; n=22, 92%, White; and n=4, 17%, physicians) to explore their experiences with the cine-VR training. Qualitative analysis revealed five themes: immersed in the virtual world: seeing a 360-degree sphere allowed participants to immerse themselves in the virtual world; facilitated knowledge acquisition: all the participants accurately recalled the culture of Appalachia and listed the social determinants of health presented in the training; empathized with multiple perspectives: the cine-VR provided a glimpse into the real life of the main character, and participants described thinking about, feeling, and empathizing with the character’s frustrations and disappointments; perceived ease of use of cine-VR: 96% (23/24) of the participants described the cine-VR as easy to use, and they liked the 360-degree movement, image resolution, and sound quality but noted limitations with the buttons on the headsets and risk for motion sickness; and perceived utility of cine-VR as a teaching tool: participants described cine-VR as an effective teaching tool because it activated visual and affective learning for them. Conclusions Participants emphasized the realism of the cine-VR training program. They attributed the utility of the cine-VR to visual learning in conjunction with the emotional connection to the VR characters. Furthermore, participants reported that the cine-VR increased their empathy for people. More research is needed to confirm an association between the level of immersion and empathy in cine-VR training for health care professionals.