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Purpose: The purpose of this study was to identify the causal relationship between emotional intelligence, ego-resilience, coping efficacy, and academic stress. Methods: Participants were 424 medical students from four medical schools in Korea. We examined their emotional intelligence, ego-resilience, coping efficacy, and academic stress using a t-test, an analysis of variance, correlational analysis, and path analysis. Results: First- and second-year students scored higher on academic stress than did those from third- and fourth-year students. Further, coping efficacy mediated the relationships between emotional intelligence, ego-resilience, and academic stress. Academic stress was directly influenced by coping efficacy, and indirectly by emotional intelligence and ego-resilience. This showed that coping efficacy play an important role in academic stress. Conclusion: Our findings may help medical schools design educational programs to improve coping efficacy in students, and to reduce their academic stress.