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Background: Education is urgently needed to equip medical students with knowledge, values and skills to promote planetary health. However, the current literature offers little insight into evidence-based approaches and best practices. In response to this pressing need, a novel serious game was introduced into the medical curriculum at Erasmus Medical Center in 2023. The aim of this study was to evaluate the knowledge and attitudes of medical students after they had played a serious game that addresses climate change and health. Methods: In accordance with a mixed-methods design, quantitative data were collected using pre- and post-intervention surveys. Differences were assessed using the Wilcoxon signed rank test. Focus group discussions were held after the game and thematically analysed. Results: One hundred forty-five students (38.6% of the entire cohort) played the game, of which 59 students completed the pre- and post-intervention surveys. After the game, self-reported knowledge increased. Regarding objective knowledge, an increase in the proportion of students who answered one of the two questions correctly was observed, while the proportion of correct responses decreased for the other question. Student's responses to two out of five attitude questions were significantly more positive. The proportion of students who recognized the importance of climate change education, to inform patients and society about the health impacts of climate change, increased. Moreover, survey results indicated a significant increase in climate worry subsequent to the game. Eleven students participated in the focus group discussions. Thematic analysis highlighted participants' reflections on the roles and responsibilities in climate change and health, along with their realisation of the tools for action that climate and health co-benefits provide. Another significant aspect was the importance participants placed on learning alongside peers with diverse attitudes. Additionally, participants appreciated the tangible overview of climate change and health provided by the serious game. Conclusions: Our novel serious game addressed an important gap in the medical curriculum. The game can enable medical students to cultivate the necessary knowledge and attitudes to promote health in times of a climate crisis. The accompanying climate worry needs attention through the empowerment of students' agency to foster change. [ABSTRACT FROM AUTHOR]