BACKGROUND: Visualization technology is enhancing interactive learning by merging digital content with real-world environments, offering immersive experiences through augmented reality (AR) in fields like medical education. AR is being increasingly used in medicine and dental education to improve student learning, particularly in understanding complex concepts such as bone remodeling. Active learning strategies, supported by AR, boost student autonomy, reduce cognitive load, and improve learning outcomes across various disciplines. AR is gaining popularity in higher education as it enhances active learning, reduces cognitive load, and improves cognitive, meta-cognitive, and affective outcomes, particularly in medical and nursing education. The effectiveness of immersive AR in enhancing understanding of complex physiological processes is still unclear, with a lack of rigorous studies on its impact and how to effectively convert academic content into AR. OBJECTIVE: We assess the capacity of AR-enhanced content for learning medical knowledge with a state-of-the-art AR game published along with a modern cell atlas of the oral cavity. To assess AR-enhanced content for learning, we formulated hypotheses on the general impact on learning (H1), specific improvements in learning (H2), and long-term retention (H3). METHODS: An AR serious game was developed to represent current knowledge on osteoclasts for classroom use. The game was evaluated in an unblinded face-to-face vignette experiment (39 participants). Learning outcomes on "Osteoclasts" were compared between the AR game (17 participants) and a textbook-only option (20 participants) conveying the same content. Participants were randomly assigned and learning success was measured at three time-points, immediately after the experiment session, 1 week later, and 1 month later, via web-based surveys. RESULTS: The AR serious game elicited strong interest in the topic (perceived relevance in Attention, Relevance, Confidence, and Satisfaction [ARCS], W=10,417; P<.001) and motivated students by increasing self-efficacy (confidence in ARCS, W=11,882.5; P=.02) and satisfaction (in ARCS, W=4561; P<.001). The learning outcomes were comparable to text-based self-learning (t=2.0103; PBonferroni=.095). Furthermore, curious students benefited more from interactive learning methods compared with text-only methods and had higher learning success (t=-2.518; P=.02). CONCLUSIONS: Introducing new technology such as AR into teaching requires technological investment, updated curricula, and careful application of learning paradigms. We found support for improved motivation (H1) and some evidence of AR's baseline effectiveness (H2a). While we could not confirm AR's impact on visual tasks overall (H2b), we noted an interesting interaction between curiosity and visual task outcomes (H2c), as well as how game design influences student perception of the material (H2d). Due to attrition, long-term learning outcomes (H3) could not be assessed. AR-based learning may particularly benefit curious students, who often struggle with text-heavy methods. As students are increasingly accustomed to brief, engaging content, teaching approaches must adapt.