Background and objective: Human research ethics committees provide essential review of research projects to ensure the ethical conduct of human research. Several recent reports have highlighted a complex process for successful application for human research ethics committee approval, particularly for multi-centre studies. Limited resources are available for the execution of human clinical research in Australia and around the world. Methods: This report overviews the process of ethics approval for a National Health and Medical Research Council-funded multi-centre study in Australia, focussing on the time and resource implications of such applications in 2007 and 2008. Results: Applications were submitted to 16 hospital and two university human research ethics committees. The total time to gain final approval from each committee ranged between 13 and 77 days (median = 46 days); the entire process took 16 months to complete and the research officer's time was estimated to cost $A34 143. Conclusions: Obstacles to timely human research ethics committee approval are reviewed, including recent, planned and potential initiatives that could improve the ethics approval of multi-centre research.