Introduction: Training emergency care skills is critical for patient safety but cost intensive. Serious games have been proposed as an engaging self-directed learning tool for complex skills. The objective of this study was to compare the cognitive skills and motivation of medical residents who only used a course manual as preparation for classroom training on emergency care with residents who used an additional serious game. Methods: This was a quasi-experimental study with residents preparing for a rotation in the emergency department. The "reading" group received a course manual before classroom training; the "reading and game" group received this manual plus the game as preparation for the same training. Emergency skills were assessed before training (with residents who agreed to participate in an extra pretraining assessment), using validated competency scales and a global performance scale. We also measured motivation. Results: All groups had comparable important characteristics (eg, experience with acute care). Before training, the reading and game group felt motivated to play the game and spent more self-study time (+2.5 hours) than the reading group. Game-playing residents showed higher scores on objectively measured and self-assessed clinical competencies but equal scores on the global performance scale and were equally motivated for training, compared with the reading group. After the 2-week training, no differences between groups existed. Conclusions: After preparing training with an additional serious game, residents showed improved clinical competencies, compared with residents who only studied course material. After a 2-week training, this advantage disappeared. Future research should study the retention of game effects in blended designs. (Sim Healthcare 12:9-16, 2017) Key Words: serious game, game-based simulation, emergency care training, clinical skills training, motivation.Heal th care, with its exponential growth in knowledge and increasing demands on the competencies required of doctors, has a need for new and more cost-effective training models. 1 Online learning, together with an instructor-led course or as a fully online course, can be used to improve the efficiency and flexibility of medical training. 1,2 Technology-enhanced simulation programs provide learning opportunities for controlled skills practice, without risk to the patient. 3 The effectiveness of simulation programs is well established. Their use in medical education is consistently associated with large improvements in knowledge, skills, and attitudes when compared with no intervention. [3][4][5] However, full-scale computer-based simulators are often expensive, both in terms of initial purchase price and running costs. 6 Furthermore, attention to student motivation is often neglected in simulation programs. 7 As a result, learners tend to use them to reach certain learning outcomes but avoid continuous practice. 8 Serious games offer a challenging learning environment in which video game characteristics are attuned to ed...