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Objective: The harmful use of alcohol is a global issue. This study aimed to describe and compare the profiles, emergency department (ED) clinical characteristics, and outcomes of alcohol-related ED presentations (ARPs) and non-alcohol-related ED presentations (NARPs). Methods: A multi-site observational study of all presentations to four EDs between 4 April 2016 and 31 August 2017, was conducted. Routinely collected ED clinical, administrative and costings data were used. Classification of ARPs were prospectively recorded by clinicians. Analysis was performed at the presentation, rather than person level. Univariate tests were undertaken to compare demographics, ED clinical characteristics and outcomes between ARPs and NARPs. Results: A total of 418 051 ED presentations occurred within the 17-month study period; 5% (n = 19 875) were ARPs. Presentations made by people classified as ARPs were younger, more likely to be male, present on weekends or at night, and arrive by ambulance or police compared to NARPs. Compared with NARPs, ARPs had a longer median ED length of stay of over 20 min (95% CI 18–22, median 196 min vs 177 min, P < 0.001), a 5.5% (95% CI 4.9–5.3) lower admission rate (36% vs 42%, P < 0.001), and a AUD69 (95% CI 64–75) more expensive ED episode-of-care (AUD689 vs AUD622, P < 0.001). Conclusion: Clinically meaningful differences were noted between alcohol-related and non-alcohol-related ED presentations. The higher cost of care for ARPs likely reflects their longer time in the ED. The healthcare and economic implications of incidents of alcohol-related harm extend beyond the ED, with ARPs having higher rates of ambulance and police use than NARPs. What is known about the topic? The harmful use of alcohol is a major health issue globally contributing to morbidity and mortality. What does this paper add? The demographic profile, clinical characteristics, and outcomes of people presenting to emergency departments with alcohol-related harm differ to people arriving for other reasons. What are the implications for practitioners? Indicating alcohol as a cause of an ED presentation, as standard practice, may foster quality assurance/improvement activities. [ABSTRACT FROM AUTHOR]