OBJECTIVE: To describe patterns and characteristics of emergency department (ED) presentations related to the use of ecstasy and related drugs (ERDs) in Melbourne, Australia. METHODS: Retrospective audit of ERD-related presentations from 1 January 2008 to 31 December 2010 at two tertiary hospital EDs. Variation in presentations across years was tested using a two-tailed test for proportions. Univariate and multivariate logistic regressions were used to compare sociodemographic and clinical characteristics across groups. RESULTS: Most of the 1347 presentations occurred on weekends, 24:00-06:00. Most patients arrived by ambulance (69%) from public places (42%), private residences (26%) and licensed venues (21%). Ecstasy-related presentations decreased from 26% of presentations in 2008 to 14% in 2009 (p<0.05); γ-hydroxybutyrate (GHB) presentations were most common overall. GHB presentations were commonly related to altered conscious state (89%); other presentations were due to psychological concerns or nausea/vomiting. Compared with GHB presentations, patients in ecstasy-related presentations were significantly less likely to require intubation (OR 0.04, 95% CI 0.01 to 0.18), but more likely to result in hospital admission (OR 1.77, 95% CI 1.08 to 2.91). Patients in amphetamine-related cases were older than those in GHB-related cases (median 28.4 years vs 23.9 years; p<0.05), and more likely to have a history of substance use (OR 4.85, 95% CI 3.50 to 6.74) or psychiatric illness (OR 6.64, 95% CI 4.47 to 9.87). Overall, the median length of stay was 3.0 h (IQR 1.8-4.8), with most (81%) patients discharged directly home. CONCLUSIONS: Although the majority of ERD-related presentations were effectively treated, with discharge within a short time frame, the number and timing of presentations places a significant burden on EDs. ERD harm reduction and improved management of minor harms at licensed venues could reduce this burden.