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Healthcare professionals practicing in the Emergency Department (ED) play a critical role in providing care in our societies. They interact with an assortment of sub-systems of the hospital and collaborate with various specialties across inpatient and outpatient settings. Research shows that >60% of ED physicians report burnout and, thus, it is important to understand the key factors contributing to their burnout. Over a ten-week period we used a mixed-method, theory-based, participatory, and data-driven approach based on survey, focus groups, and contextual inquiries to collect and analyze data and prioritize improvement efforts. Key areas of improvement were: i) workflows and patient monitoring that add to high cognitive load and stress levels; ii) low staffing, particularly among sitters, nurses, technicians, secretaries, and security staff; iii) suboptimal therapeutic atmosphere for psychiatric patients; iv) disrespectful and violent patients and visitors; v) communication issues, especially between the ED and other departments; and vi) frequent problems with the telecommunication system. We learned that EDs must take time to rigorously evaluate contributing factors to burnout while engaging their people who best know how to change systems to achieve positive and sustainable results.