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Background: Clinical reasoning is a complex skill students have to acquire duringtheir education. For educators it is difficult to explain their reasoningto students, because it is partly an automatic and unconscious process. Virtual Patients (VPs) are used to support the acquisition of clinical reasoning skills in healthcare education. However, until now it remains unclear which features or settings of VPs optimally foster clinical reasoning. Therefore, our aims were to identify key concepts of the clinical reasoning process in a qualitative approach and draw conclusions on how each concept can be enhanced to advance the learning of clinical reasoning with virtual patients. Methods: We chose a grounded theory approach to identify key categories and concepts of learningclinical reasoningand develop a framework. Throughout this process, the emerging codes were discussed with a panel of interdisciplinary experts. In a second step we applied the framework to virtual patients. Results: Based on the data we identified the core category as the "multifactorial nature of learning clinical reasoning". This category is reflected in the following five main categories: Psychological Theories, Patient-centeredness, Context, Learner-centeredness, and Teaching/Assessment. Each category encompasses between four and six related concepts. Conclusions: With our approach we were able to elaborate how key categories and concepts of clinical reasoning can be applied to virtual patients. This includes aspects such as allowing learners to access a large number of VPs with adaptable levels of complexity and feedback or emphasizing dual processing, errors, and uncertainty. [ABSTRACT FROM AUTHOR]