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By applying an explorative approach, we aimed to identify a wide set of challenges and opportunities for the compatibility of the work and life domains in emergency department (ED) physicians as well as their suggestions for practical approaches to improve work-life balance. Four focus groups with 14 physicians of differing hierarchical position and family status were carried out at two EDs of one major university hospital. Data analysis was based on qualitative content analysis. Discussed themes within main categories included ED work conditions, aspects of residency training, physician’s mentality and behaviors as well as context factors of university medicine. Working in an ED is associated with a comparatively high work-life-interference, mostly due to the unpredictable nature of ED work. Based on our context-specific findings, further research might address factors influencing work-life balance in ED physicians with a mixed-methods approach for identification of relevant associations and intervention approaches in this field.