Background: This economic evaluation reports the results of a detailed study of the cost of major trauma treated at Princess Alexandra Hospital (PAH), Australia. Methods: A bottom-up approach was used to collect and aggregate the direct and indirect costs generated by a sample of 30 inpatients treated for major trauma at PAH in 2004. Major trauma was defined as an admission for Multiple Significant Trauma with an Injury Severity Score 15. Direct and indirect costs were amalgamated from three sources, (1) PAH inpatient costs, (2) Medicare Australia, and (3) a survey instrument. Inpatient costs included the initial episode of inpatient care including clinical and outpatient services and any subsequent representations for ongoing-related medical treatment. Medicare Australia provided an itemized list of pharmaceutical and ambulatory goods and services. The survey instrument collected out-of-pocket expenses and opportunity cost of employment forgone. Inpatient data obtained from a publically funded trauma registry were used to control for any potential bias in our sample. Costs are reported in Australian dollars for 2004 and 2008. Results: The average direct and indirect costs of major trauma incurred up to 1-year postdischarge were estimated to be A$78,577 and A$24,273, respectively. The aggregate costs, for the State of Queensland, were estimated to range from A$86.1 million to $106.4 million in 2004 and from A$135 million to A$166.4 million in 2008. Conclusions: These results demonstrate that (1) the costs of major trauma are significantly higher than previously reported estimates and (2) the cost of readmissions increased inpatient costs by 38.1%.