BACKGROUND Identifying preoperative patient characteristics that correlate with an increased risk of periprosthetic joint infection (PJI) following total ankle replacement (TAR) is of great interest to orthopaedic surgeons, as this may assist with appropriate patient selection. The purpose of this study is to systematically review the literature to identify risk factors that are associated with PJI following TAR. METHODS Utilizing the terms "(risk factor OR risk OR risks) AND (infection OR infected) AND (ankle replacement OR ankle arthroplasty)" we searched the PubMed/MEDLINE electronic databases. The quality of the included studies was then assessed using the AAOS Clinical Practice Guideline and Systematic Review Methodology. Recommendations were made using the overall strength of evidence. RESULTS Eight studies met the inclusion criteria. A limited strength of recommendation can be made that the following preoperative patient characteristics correlate with an increased risk of PJI following TAR: inflammatory arthritis, prior ankle surgery, age less than 65 years, body mass index less than 19, peripheral vascular disease, chronic lung disease, hypothyroidism, and low preoperative AOFAS hindfoot scores. There is conflicting evidence in the literature regarding the effect of obesity, tobacco use, diabetes, and duration of surgery. CONCLUSIONS Several risk factors were identified as having an association with PJI following TAR. These factors may alert surgeons that a higher rate of PJI is possible. However, because of the low level of evidence of reported studies, only a limited strength of recommendation can be ascribed to regard these as risk factors for PJI at this time.