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Perioperative hyperglycemia has many etiologies, including medication, impaired glucose tolerance, uncontrolled diabetes mellitus, or stress, the latter of which is common in patients postoperatively. Our study investigated the influence of postoperative blood glucose levels on periprosthetic joint infection after elective total joint arthroplasty to determine a threshold for glycemic control for which surgeons should strive during a patient’s hospital stay.A single-institution retrospective review was conducted on 24,857 primary total joint arthroplasties performed from 2001 to 2015. Of these, 13,196 had a minimum follow-up of 1 year (mean, 5.9 years). Postoperative day 1 morning blood glucose levels were utilized and were correlated with periprosthetic joint infection, as defined by the International Consensus Group on Periprosthetic Joint Infection. Multivariable analysis was used to determine the influence of several important covariates on infection. An alpha level of 0.05 was used to determine significance.The rate of periprosthetic joint infection increased linearly from blood glucose levels of ≥115 mg/dL. Multivariable analysis revealed that blood glucose levels were significantly associated with periprosthetic joint infection (p = 0.028). The optimal blood glucose threshold to reduce the likelihood of periprosthetic joint infection was 137 mg/dL. The periprosthetic joint infection rate in the entire cohort was 1.59% (1.46% in patients without diabetes compared with 2.39% in patients with diabetes; p = 0.001). There was no significant association between blood glucose level and periprosthetic joint infection in patients with diabetes (p = 0.276), although there was a linear trend.The relationship between postoperative blood glucose levels and periprosthetic joint infection increased linearly, with an optimal cutoff of 137 mg/dL. Immediate and strict postoperative glycemic control may be critical in reducing postoperative complications, as even mild hyperglycemia was significantly associated with periprosthetic joint infection.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.