Abstract Introduction Over the past decade, the incidence of revision arthroplasty has increased substantially. One of the main reasons for revision arthroplasty is periprosthetic joint infection, often resulting in multiple surgical interventions with variable success and poor clinical outcome. Intraoperative wound irrigation has been proposed to reduce bacterial contamination and thus the risk of periprosthetic infection. However, there is currently no widely accepted recommendation for the use of topical antiseptics within the operative setting for primary implantation. We performed a systematic review of studies pertaining to the use of intraoperative topical antiseptics and their effectiveness in preventing infection of orthopaedic implants. Materials and Methods A comprehensive literature search including MEDLINE (PubMed), Cochrane Library, and Current Contents Medicine (CCMED-Medpilot) was performed according to a standardised protocol. Results Overall, 1905 articles were initially assessed. Four studies met the inclusion criteria and remained for further analysis, comprising two prospective cohort studies using retrospective control groups (evidence level II – III) and two randomised controlled trials (evidence level I). 0.35% Povidone-iodine (PVP-I) was used in three of these studies and a solution of 6.25% PVP-I and 6.25%-hydrogen peroxide (H2O2) in one study for intraoperative wound irrigation. There was a clear trend in all studies suggesting that intraoperative topical antiseptics are effective in preventing periprosthetic infection. Conclusion Although no clear regimen can be recommended, the available literature indicates that the use of intraoperative topical antiseptics is of clinical relevance in preventing infection of orthopaedic implants. Further randomised controlled trials are recommended.