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The impact of perioperative hyperglycemia in orthopaedic surgery is not well defined. We hypothesized that hyperglycemia is an independent risk factor for thirty-day surgical-site infection in orthopaedic trauma patients without a history of diabetes at hospital admission.Patients eighteen years of age or older with isolated orthopaedic injuries requiring acute operative intervention were studied. Patients with diabetes, injuries to other body systems, a history of corticosteroid use, or admission to the intensive care unit were excluded. Blood glucose values were obtained, and hyperglycemia was defined in two ways. First, patients with two or more blood glucose levels of ≥200 mg/dL were identified. Second, the hyperglycemic index, a validated measure of overall glucose control during hospitalization, was calculated for each patient. A hyperglycemic index of ≥1.76 (equivalent to ≥140 mg/dL) was considered to indicate hyperglycemia. The primary outcome was thirty-day surgical-site infection. Multivariable logistic regression models evaluating the effect of the markers of hyperglycemia, after controlling for open fractures, were constructed.Seven hundred and ninety patients were identified. There were 268 open fractures (33.9%). Twenty-one thirty-day surgical-site infections (2.7%) were recorded. Age, race, comorbidities, injury severity, and blood transfusion were not associated with the primary outcome. Of the 790 patients, 294 (37.2%) had more than one glucose value of ≥200 mg/dL. This factor was associated with thirty-day surgical-site infection, with thirteen (4.4%) of the 294 patients with that indication of hyperglycemia having a surgical-site infection versus eight (1.6%) of the 496 patients without more than one glucose value of ≥200 mg/dL (p = 0.02). One hundred and thirty-four (17.0%) of the 790 patients had a hyperglycemic index of ≥1.76, and this was also associated was thirty-day surgical-site infection (ten [7.5%] of 134 versus eleven [1.7%] of 656; p < 0.001). Multivariable logistic regression models demonstrated that two or more blood glucose levels of ≥200 mg/dL was a risk factor for thirty-day surgical-site infection (odds ratio [OR]: 2.7, 95% confidence interval [CI]: 1.1 to 6.7) after adjustment for open fractures (OR: 3.2, 95% CI: 1.3 to 7.8). A second model demonstrated that a hyperglycemic index of ≥1.76 was an independent risk factor for surgical-site infection (OR: 4.9, 95% CI: 2.0 to 11.8) after controlling for open fractures (OR: 3.3, 95% CI: 1.4 to 8.3).Hyperglycemia was an independent risk factor for thirty-day surgical-site infection in orthopaedic trauma patients without a history of diabetes.Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.