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Background: Graduate education in modern diplomacy poses several challenges, as it requires several competencies to be developed before diplomatic service is joined. Incorporation of simulation games can have a positive impact on the design of international relations and diplomacy learning process. We have designed a novel role play game (MAEDRI) to simulate part of the activities of a typical Ministry of Foreign Affairs., Objective: This study aims to evaluate the effectiveness of MAEDRI in transferring knowledge in international relations education programs at the National University of Political Studies and Public Administration, Bucharest, Romania, across a 4-year period., Methods: The game enrolled master's level graduate students. The data were collected through a voluntary and anonymous questionnaire between 2017 and 2020. At the end of each of the 4 editions we organized debriefing sessions that gave students the opportunity to provide feedback on their experience with this exercise, level of collaboration within the team, lessons learned, and to make suggestions for improvements. Using an online questionnaire, we measured the participants' perception regarding the level of effectiveness in increasing knowledge transfer, motivation, and engagement. Questionnaire data were consolidated in percentages for each item., Results: A total of 49 participants completed the study. A total of 24 skills (13 professional and 11 social skills) were assessed. We identified a strong positive correlation between stress management and conflict management (r=.86; P<.001) as well as significantly positive correlations between building relations within the team and the ability to dialog and be persuasive (r=.7; P<.001), between procedure compliance and planning and organizing the work (r=.69; P<.001), and between analysis capacity and decision based on data received (r=.68; P<.001). Among social skills, self-control, confidence, and flexibility were the most substantially improved., Conclusions: We describe several benefits of a novel game, used as an education tool to enhance a series of competencies necessary in international relations studies. Our results demonstrate a significant level of student engagement and motivation while playing MAEDRI, improvement of several essential skills, and enhanced knowledge transfer to real-life situations. While the data are encouraging, further research is needed to evaluate the full impact of role play as an effective experiential learning method., (©Mihai Ovidiu Cercel. Originally published in JMIR Serious Games (https://games.jmir.org), 25.04.2022.)