Abstract 
Background Emergency departments (EDs) are the frontline of acute care in the USA, yet contemporary data on the most common presentations and causes of mortality remain limited. Understanding these patterns is critical for guiding triage, resource allocation and public health priorities. Therefore, using a nationally representative sample of US ED visits from 2016 to 2021, this study aimed to characterise the most common ED diagnoses and leading causes of ED mortality and to assess differences in these patterns across age, sex, race/ethnicity and urban-rural populations.
Methods We conducted a retrospective cohort study of the Nationwide Emergency Department Sample from 2016 to 2021, encompassing more than 680 million weighted ED visits. Outcomes included the five most common presenting diagnoses and causes of ED mortality, stratified by age, sex, race/ethnicity and urban-rural status. Diagnoses were grouped into clinically relevant categories, including acute coronary syndromes (ACS), severe respiratory compromise, trauma and sepsis.
Results During 2016–2021, there were 680 207 479 ED visits and 1 189 848 ED deaths. Chest pain was the leading diagnosis from 2016 to 2019 (4.3–4.4%); in 2021, COVID-19 became the most common presentation (4.8% vs 4.2% for chest pain). Urinary tract infections were more frequent in women (2.6%), whereas sepsis was more common in men (1.6%). Younger adults presented with respiratory infections, abdominal pain and headaches, while older adults had higher rates of sepsis, chronic obstructive pulmonary disease exacerbations and pneumonia. Racial differences were evident: COVID-19 was most frequent in Hispanic patients (3.4%), sepsis in Asian/Pacific Islanders (2.1%) and alcohol intoxication in Native Americans (2.0%). Cardiac arrest was the leading cause of ED death (58–77%). Trauma (7.9%) and self-harm (0.8%) disproportionately affected younger adults, whereas sepsis (up to 2.7%), respiratory compromise (up to 3.7%) and ACS (0.6–1.4%) contributed more to mortality among older adults, women and racial minorities.
Conclusion This national analysis highlights evolving ED utilisation, COVID-19 impact and persistent age-based, sex-based and race-based disparities. Although cardiac arrest dominates ED mortality, the excess burden of sepsis, respiratory failure, ACS, trauma and self-harm in specific populations underscores opportunities to refine triage, target prevention and improve emergency care allocation.
