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Introduction: Gamma‐hydroxybutyrate (GHB) use is associated with high risk of accidental overdose. This study examined the pre‐hospital circumstances, demographic characteristics and clinical outcomes of analytically confirmed GHB emergency department (ED) presentations in Western Australia (WA). Methods: This case series was conducted across three WA EDs involved in the Emerging Drugs Network of Australia, from April 2020 to July 2022. Patient demographics, pre‐hospital drug exposure circumstances and ED presentation and outcome characteristics were collected from ambulance and hospital medical records of GHB‐confirmed cases. Results: GHB was detected in 45 ED presentations. The median age was 34 years and 53.3% (n = 24) were female. Most patients arrived at the ED by ambulance (n = 37, 85.7%) and required immediate emergency care (Australasian Triage Score 1 or 2 = 97.8%). One‐third of patients were admitted to intensive care (n = 14, 31.1%). Methylamphetamine was co‐detected in 37 (82.2%) GHB‐confirmed cases. Reduced conscious state was indicated by first recorded Glasgow Coma Scale of ≤8 (n = 29, 64.4%) and observations of patients becoming, or being found, 'unresponsive' and 'unconscious' in various pre‐hospital settings (n = 28, 62.2%). 'Agitated' and/or 'erratic' mental state and behavioural observations were recorded in 20 (44.4%) cases. Discussion and Conclusions: Analytically verified data from ED presentations with acute toxicity provides an objective information source on drug use trends and emerging public health threats. In our study, patients presenting to WA EDs with GHB intoxication were acutely unwell, often requiring intensive care treatment. The unexpectedly high proportion of female GHB intoxications and methylamphetamine co‐ingestion warrants further exploration. [ABSTRACT FROM AUTHOR]