BACKGROUND : Medication reconciliation (medrec) is a mandated patient safety strategy by national, including Australian, accreditation bodies. Yet there are no validated performance measures. OBJECTIVE : To determine the feasibility of implementing the World Health Organization (WHO) Medrec Standard Operating Protocol (SOP) in a range of Australian acute care facilities to achieve measurable and sustainable reductions in medication discrepancies occurring at admission. METHODS : A multicentre, prospective national study was conducted in ten academic, urban and regional hospitals to implement the SOP using WHO High 5s project and quality improvement methodology. Sites collected data on the rate of medrec performed within 24 h of admission in a random selection of 50 patients aged ≥65 years admitted via the emergency department, monthly for four years. Medrec quality was reviewed in a subset of 30 patients using three performance measures. Barriers, enablers and benefits of SOP implementation were collected using qualitative surveys. RESULTS : Ten health services reviewed 42,003 patient records. Of these, 20,162 (49.5%) had medicines reconciled within 24 h of admission. Four services increased, two decreased, and in four, medrec completion rates remained static. Mean number of unintentional and undocumented intentional medication discrepancies per patient decreased: 0.21 to 0.16 (p = 0.001) and 0.34 to 0.08 (p = 0.003), respectively. Unintentional discrepancies decreased from 15.2% to 11.1% (p = 0.001). Barriers to full implementation included: medrec not seen as a priority, limited resources and lack of electronic systems integration. Enablers included: use of medrec measures for feedback, educational resources, and 7-day week clinical pharmacy services. Benefits included improvements in medication safety culture and multidisciplinary teamwork. CONCLUSIONS : The WHO SOP was feasible, although challenging, to implement in a range of acute health services, and produced measureable and sustainable improvements in medicines information accuracy on admission. Sustaining the quantum of quality and timely medrec requires investment in pharmacist resources and electronic systems integration.