Objectives: To evaluate the short-term mortality of adult patients presenting to the emergency department (ED) with altered mental status (AMS) as compared to other common chief complaints., Methods: Observational cohort study of adult patients (age ≥ 40) who presented to an academic ED over a 1-year period with five pre-specified complaints at ED triage: AMS, generalized weakness, chest pain, abdominal pain, and headache. Primary outcomes included 7 and 30-day mortality. Hazard ratios (HR) were calculated with 95% confidence intervals (CI) using Cox proportional hazards models adjusted for age, acuity level, and comorbidities., Results: A total of 9850 ED visits were included for analysis from which 101 (1.0%) and 295 (3.0%) died within 7 and 30 days, respectively. Among 683 AMS visits, the 7-day mortality rate was 3.2%. Mortality was lower for all other chief complaints, including generalized weakness (17/1170, 1.5%), abdominal pain (32/3609, 0.9%), chest pain (26/3548, 0.7%), and headache (4/840, 0.5%). After adjusting for key confounders, patients presenting with AMS had a significantly higher risk of death within 7 days of ED arrival than patients presenting with chest pain (HR 3.72, 95% CI 2.05 to 6.76, p < .001). Similarly, we found that patients presenting with AMS had a significantly higher risk of dying within 30 days compared to patients with chest pain (HR 3.65, 95% CI 2.49 to 5.37, p < .001), and headache (HR 2.09, 95% CI 1.09 to 4.01, p = .026). Differences were not statistically significant for comparisons with abdominal pain and generalized weakness, but confidence intervals were wide., Conclusion: Patients presenting with AMS have worse short-term prognosis than patients presenting to the ED with chest pain or headache. AMS may indicate an underlying brain dysfunction (delirium), which is associated with adverse outcomes and increased mortality., Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflict of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)