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Preoperative identification of patients at risk for periprosthetic joint infection (PJI) following total hip arthroplasty (THA) or total knee arthroplasty (TKA) is important for patient optimization and targeted prevention. The purpose of this study was to create a preoperative PJI risk calculator for assessing a patient’s individual risk of developing (1) any PJI, (2) PJI caused by Staphylococcus aureus, and (3) PJI caused by antibiotic-resistant organisms.A retrospective review was performed of 27,717 patients (12,086 TKAs and 31,167 THAs), including 1,035 with confirmed PJI, who were treated at a single institution from 2000 to 2014. A total of 42 risk factors, including patient characteristics and surgical variables, were evaluated with a multivariate analysis in which coefficients were scaled to produce integer scores. External validation was performed with use of data on 29,252 patients who had undergone total joint arthroplasty (TJA) at an independent institution.Of the 42 risk factors studied, 25 were found not to be significant risk factors for PJI. The most influential of the remaining 17 included a previous open surgical procedure, drug abuse, a revision procedure, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). The areas under the curves were 0.83 and 0.84 for any PJI, 0.86 and 0.83 for antibiotic-resistant PJI, and 0.86 and 0.73 for S. aureus PJI in the internal and external validation models, respectively. The rates of PJI were 0.56% and 0.61% in the lowest decile of risk scores and 15.85% and 20.63% in the highest decile.In this large-cohort study, we were able to identify and validate risk factors and their relative weights for predicting PJI. Factors such as prior surgical procedures and high-risk comorbidities should be considered when determining whether TJA is indicated and when counseling patients.Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.