OBJECTIVE: The objective of this review was to synthesize the best evidence for the effectiveness of interventions to reduce occupational stress and/or burnout in the emergency department. INTRODUCTION: The prevalence of occupational stress and burnout among busy emergency department staff requires urgent attention. This review summarizes the current evidence to provide recommendations on interventions to reduce occupational stress in the emergency department. INCLUSION CRITERIA: Studies reporting on all health personnel working in emergency departments were included in the review. Any individual-focused or organizational-directed intervention was considered. Both published and unpublished studies including experimental and quasi-experimental studies were considered for inclusion in the review. The outcomes of interest included occupational stress, burnout, compassion fatigue, anxiety, and depression. METHODS: A three-step search strategy was utilized to search seven databases (PubMed, CINAHL, Cochrane Central Register of Controlled Trials, Embase, Scopus, PsycINFO, Web of Science) and five gray literature resources (MedNar, Google Scholar, ProQuest Dissertations and Theses, Conference Proceedings). The search was limited to papers published in English between January 1, 2008, and February 1, 2019. Titles and abstracts of the studies were screened. Two reviewers independently appraised the full text of selected studies and extracted data using standardized tools from JBI. Where possible, data were pooled in statistical meta-analysis. Effect sizes were expressed as standardized mean differences, and their 95% confidence intervals were calculated for analysis. RESULTS: A total of 14 studies were included in the systematic review. Sample sizes of the included studies ranged from 14 to 392 participants. Of the included studies, four were randomized controlled trials and 10 were quasi-experimental studies. The overall quality of the included studies was compromised due to lack of true randomization, concealment, blinding, or the use of a single-group without a comparator. Educational-style interventions were investigated in six included studies and mindfulness-based interventions in four studies. The remaining four studies investigated organizational-directed interventions that incorporated a variety of strategies. The top three most commonly used tools were the Maslach Burnout Inventory, the Perceived Stress Scale, and the Professional Quality of Life Scale. The studies that investigated educational interventions reported a statistically significant reduction in both stress and/or burnout. Three of the four studies that investigated mindfulness-based interventions reported reduced stress levels. A fixed-effects meta-analysis of two of the studies demonstrated a non-significant difference in stress between groups receiving mindfulness-based interventions and those who did not (n = 58, SMD = -0.32, 95% CI -0.84 to 0.20, P = 0.23; heterogeneity: x = 0.01, P = 0.93, I = 0%). Organizational-based interventions were found to reduce stress levels but increase burnout. CONCLUSIONS: Individual-focused interventions, including both educational interventions and mindfulness-based interventions, have the potential to reduce occupational stress and/or burnout for staff working in emergency departments. However, inconsistencies in reporting and outcome measurements impact certainty of results. More high-quality randomized controlled trials are recommended with larger sample sizes as well as measurement of long-term effects to improve knowledge in this field.