Background: Periprosthetic joint infection (PJI) represents 25% of failed total knee arthroplasties (TKA). The European Knee Associates (EKA) formed a transatlantic panel of experts to perform a literature review examining patient-related risk factors with the objective of producing perioperative recommendations in PJI high-risk patients. Methods: Multiple databases (Pubmed/MEDLINE, EMBASE, Scopus, Cochrane Library) and recommendations on TKA PJI prevention measures from the International Consensus Meetings on PJI from the AAOS and AAHKS were reviewed. This represents a Level IV study. Results: Strong evidence was found on poor glycemic control, obesity, malnutrition, and smoking being all associated with increased rates of PJI. In the preoperative period, patient optimization is key: BMI < 35, diet optimization, Hemoglobin A1c < 7.5, Fructosamine < 292 mmol/L, smoking cessation, and MRSA nasal screening all showed strong evidence on reducing PJI risk. Intraoperatively, a weight-based antibiotic prophylaxis, accurate fluid resuscitation, betadine and chlorhexidine dual skin preparation, diluted povidone iodine solution irrigation, tranexamic acid administration, and monofilament barbed triclosan-coated sutures for soft tissues closure all represented effective prevention measures. In the postoperative period, failure to reach normalization of ESR, CRP, D-dimer, and IL-6 six weeks postoperatively suggested early PJI. Conclusion: The current recommendations from this group of experts, based on published evidence, support risk stratification to identify high-risk patients requiring implementation of perioperative measures to reduce postoperative PJI.