Although diagnostic accuracy in the emergency department (ED) is high, diagnostic errors still occur. This evidence review estimated that 1 in 18 ED patients receive an incorrect diagnosis, which translates to 7.4 million patients misdiagnosed every year (or 5.7% of all ED visits annually). Five conditions were found to be most vulnerable to misdiagnosis: stroke, heart attack, aortic aneurysm/ dissection, spinal cord injury and blood clots. The evidence review identified variation in diagnostic error rates across demographic groups; female sex and non-White race were often associated with increased risk for diagnostic errors. Serious misdiagnosis-related harms were often associated with clinician bedside judgement and other cognitive failures.