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Purpose: This study aimed to identify the effect of job stress, coping behavior, and hardiness on burnout in nurses in the emergency department (ED). Methods: Data were acquired via self-reporting questionnaires from 148 nurses in EDs at one general hospital, four university hospitals, and six hospitals with >200 beds. Data were analyzed using the SPSS 23.0 program through descriptive statistics, t-test, analysis of variance, Pearson's correlation coefficient, and stepwise multiple regression. Results: A statistically significant difference in burnout was observed with respect to the age of the nurses. Burnout was positively correlated with job stress and wishful thinking and detachment, among coping behaviors, and was negatively correlated with hardiness. Job stress and wishful thinking, among coping behaviors, were significant predictors of burnout and were observed in 14.9% of the nurses who experienced burnout. Conclusion: According to our results, job stress was identified as the most significant factor which influenced burnout in ED nurse's. Therefore, it is necessary to develop and implement educational programs for reducing job stress and minimizing the use of wishful thinking as a coping behavior in order to alleviate the burnout in ED nurses.