This commentary reviews the principles of high reliability organizations and their application to emergency department pandemic response and describes the experience of one children’s hospital in Alberta, Canada applying these principles in responding to the COVID-19 pandemic. Actions taken by the hospital included the use of an interprofessional ED quality council to identify processes where high reliability is essential in the context of the COVID-19 pandemic, such as resuscitations, intubations, donning and doffing of personal protective equipment (PPE), and preventing contamination.