The purpose of this study was to identify the causal relationship between emotional intelligence, ego-resilience, coping efficacy, and academic stress. 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. 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. Our findings may help medical schools design educational programs to improve coping efficacy in students, and to reduce their academic stress.