Patients undergoing total joint arthroplasty (TJA) hope for an improved quality of life. With an aging global population, the demand for TJA, especially knee and hip procedures, is expected to rise significantly. While these surgeries generally lead to favorable patient outcomes, a major concern is the risk of developing a periprosthetic joint infection (PJI). PJI is a severe complication leading to increased mortality, morbidity, and significant suffering for patients. Although the individual risk of PJI is low, the increasing frequency of TJAs raises the cumulative incidence. This trend poses challenges for orthopedic surgeons and financial burdens on healthcare systems globally. To maximize the therapeutic benefit of TJA, it is of utmost importance to minimize possible complications, such as PJIs. Identifying and understanding risk factors are therefore vital. Numerous studies have mapped out risk factors for PJI. However, there are cases where PJIs occur in the absence of these known risk factors, suggesting that other mechanisms, including genetic predispositions, may be involved. Studies on familial risk of PJI have reported an increased risk among first- and second-degree relatives, which has opened the door for further genetic studies. An essential method in genetic analysis involves the examination of DNA polymorphisms, specifically single nucleotide polymorphisms (SNPs). SNPs are variations of single nucleotides occurring at known positions in the genome sequence. Some SNPs are functionally significant as they can influence how individuals respond to diseases, medications, and other environmental factors. Researching into SNPs is at the forefront of understanding disease-gene relationships. To summarize, although there are indications, substantial evidence of a genetic predisposition to PJIs is lacking, and the identification of specific SNPs that increase susceptibility remains an unmet research need. Previous studies have shown an increased familial risk of developing PJIs, indicating a potential genetic component in susceptibility to these infections. We hypothesize that this genetic predisposition exists. This study aims to determine whether carrying certain SNPs lead to an inherent risk of developing a PJI.