Objectives: To describe the profile of people who received post-exposure treatment to prevent lyssavirus infection in Sydney South West Area Health Service between 2005 and 2007 and to assess treatment compliance with the current NSW Health protocol. Methods: Thirty-eight public health files and a subset of 11 medical records were reviewed to collect demographic, exposure and treatment information for the period. Results: Twenty-nine (76%) potential Lyssavirus exposures occurred overseas. Nine potential exposures occurred within Australia; eight of these resulted from a bat bite or scratch. Thirteen (34%) of all potential exposures resulted from handling an animal. Conclusion: Many potential exposures were the result of a bite or scratch from a domesticated animal; the animal’s survival or health status was not routinely recorded. While all people who commenced post-exposure treatment completed the prescribed course, this was often not within the stipulated timeframe.