OBJECTIVE: To determine the prevalence and nature of off-label and unlicenced (off-label/unlicenced) medicine administration to paediatric ED patients. METHODS: We undertook a retrospective, observational study in six EDs (July 2011 to June 2012, inclusive). Patients, aged 0-17 years, who were administered a medicine in the ED were included. At each site, 50 eligible patients were randomly selected each month of the study period. An explicit review of each patient s records was undertaken. Medicines were classified as on or off-label/unlicenced according to categories of use approved by the Therapeutic Goods Administration. RESULTS: There were 3343 patients enrolled (56.5 men, mean +/- SD age 6.7 +/- 5.4 years). Of the 6786 medicine doses administered, 2072 (30.5 , 95 CI 29.4-31.7 ) were off-label/unlicenced. The off-label/unlicenced doses were administered to 1213 (36.3 , 95 CI 34.7-37.9 ) patients. Patients administered an off-label/unlicenced medicine were younger than those who were not (P <0.01). Salbutamol, ondansetron, ipratropium, fentanyl and oxycodone were the medicines most commonly administered off-label. In 910 (44.0 ) cases, the dose/frequency was not approved; in 592 (28.6 ), there was an unapproved indication for treatment; in 158 (7.6 ), the medicine was administered via an unapproved route; in 154 (7.4 ) the medicine was not approved for the weight or age; and in 74 (3.5 ) an unlicenced product was administered. The remaining cases had combinations of reasons. CONCLUSIONS: Off-label/unlicenced medicine administration is common. A registry of commonly used off-label medicines is recommended in which the safety and efficacy of their off-label use have been demonstrated by published evidence.