OBJECTIVE: To assess the frequency of adverse drug event (ADE)-related admissions (ADE-RAs) during a prospective medical record review of patients admitted to a metropolitan tertiary referral hospital. METHODS: Potential ADE-RA cases were identified by examination of case records of randomly selected patients. Cases were assessed by an expert panel to measure study outcomes, which were the frequency (ADEs and ADE-RAs) as well as type, likelihood of causality, severity, avoidability and detection of ADEs. RESULTS: Of the 370 subjects, 59 (16.0%) had a confirmed ADE-RA, with 15 (4.1%) of these serious and preventable. The 59 ADE-RAs were a result of 72 discreet ADEs. Adverse drug reactions were the most common type of ADE, followed by non-compliance. Of the 72 discreet ADEs, 31.9% were classified as 'probable' or 'highly probable'. Most ADEs (54.2%) were classified as 'definitely avoidable', 34.7% were classified as 'severe' and 21.8% were classified as both 'definitely avoidable' and 'severe'. Half the ADEs were detected after the patient had been admitted and most were detected by medical practitioners. Antineoplastics followed by antidiabetic agents were most frequently implicated. CONCLUSIONS: Implementing a systems approach that involves multiple strategies, such as improving tertiary-to-primary care information transfer and promoting medication adherence through education programs, is necessary to tackle the problem of avoidable ADE-RAs and the associated cost burden. WHAT IS KNOWN ABOUT THE TOPIC? It is estimated that 2-3% of Australian hospital admissions are due to adverse drug events (ADEs), but recent data are lacking. According to the Australian Statistics on Medicines, over 250 million prescriptions were dispensed in 2007, compared with just under 180 million in 1997. This 40% increase in drug utilisation over the 10 years surpasses the Australian population growth of 14% in the same period. An increase in drug use per person indicates that the rate of ADEs and possible ADE-related admissions (ADE-RAs) is likely to have increased. WHAT DOES THIS PAPER ADD? This prospective study was conducted at a large Australian metropolitan teaching hospital and we report that 59 of 370 participants (16.0%) presenting to the Emergency Department had a confirmed ADE-RA, with 15 (4.1%) presenting with a serious and preventable ADE-RA. WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? The findings of this study support implementing a systems approach involving multiple strategies to tackle the problem of avoidable ADE-RAs and the associated cost burden. This study reveals that half the ADEs were not detected until after the admission process, which reinforces the importance of focusing efforts towards preventing ADE-RAs and detecting ADE-RAs through measures such as those recommended in the Australian Pharmaceutical Advisory Council guiding principles.