OBJECTIVES: To conduct a systematic review of literature on the epidemiological and economic burden of surgical site infection (SSI) in Australia.  METHODS: A  literature search of the EMBASE and Medline databases was conducted. The search was limited to 1995–2010 to ensure the pertinence of the data. Searches to identify epidemiological and economic studies were conducted separately. Relevant studies were identified using pre-defined criteria (i.e., reports the rate, risk factors, cost of SSI; conducted in a hospital setting; not an intervention study). RESULTS: Thirty-five studies were included in this review. Differences in study design (surveillance period, data collection method, surgical procedure) made it difficult to synthesise data to derive a single estimate of SSI in Australia. The overall incidence of SSI in Australia is approximately 5–10%. However, the rate of SSI varied across different procedures: higher rates were seen following gastrointestinal (~11%) and cardiovascular (6–13%) surgery, while the rates for orthopaedic (4.7–8%) and gynaecological surgery (2.3–10%) appeared lower. Risk factors identified include diabetes and obesity, which increased the risk of SSI by 60–180%. The National Nosocomial Infections Surveillance (NNIS) risk index was positively correlated with the risk of developing an SSI. The most common organisms identified in SSIs were Staphylococcus aureus and Pseudomonas aeruginosa. The hospitalisation cost attributable to SSI is estimated at approximately AUD$54 million annually. With a large proportion of SSIs occurring after discharge from hospital, the incidence of SSI is likely underestimated. Post-discharge SSI, in turn, increases the burden to community health services. Indirect costs, such as loss of productivity, further add to the economic burden of SSI. CONCLUSIONS: The incidence and cost estimates demonstrate that SSI represents a significant burden to the Australian health care system. Interventions aimed at reducing SSI would provide cost-savings and improve the efficiency of the health care system.