Objectives Emergency department (ED) professionals are exposed to burnout syndrome due to excessive workload and high demands for care. The objective of our study was to assess the prevalence burnout among all ED staff and to determine associated factors. Methods A cross-sectional survey was conducted in 3 EDs. The data were collected using a standardized questionnaire. It included demographical and occupational data, general health questions, burnout level (Maslach Burnout Inventory), job strain (Karasek), and quality of life (Medical Outcome Study Short Form). Results Of the 529 professionals working in EDs, 379 responses were collected (participation rate of 71.6%). Emotional exhaustion (EE) and depersonalization (DP), the major components of burnout, were reported, respectively, by 15.8% and 29.6% of the professionals. Burnout prevalence was 34.6%, defined as a severely abnormal level of either EE or DP. The medical category was significantly more affected by the burnout compared with their colleagues: nearly one ED physician out of two had a burnout (50.7%). In the multivariate analysis of covariance, job strain and a low mental component score were the two main factors independently associated with burnout (p < 0.05). Conclusion The results of our study show that ED professionals are a vulnerable group. Preventive approaches to stress and burnout are needed to promote quality of work life.