Surgical site infections (SSIs) affect 1% to 9% of all spine surgeries. Though previous work has found diabetes mellitus type 2 (DM2) to increase the risk for wound infection, the influence of perioperative hyperglycemia is poorly described. To investigate perioperative hyperglycemia as an independent risk factor for surgical site infection. We retrospectively identified patients undergoing operative management of SSIs occurring after spinal surgery for degenerative pathologies. These patients were individually matched to controls based upon age, surgical invasiveness, ICD-10CM, race, and sex. Cases and controls were compared regarding medical comorbidities (including diabetes), postoperative hyperglycemia, and operative time. Patients in the infection group were found to have a higher BMI (33.7 vs 28.8), higher prevalence of DM2 (48.5% vs 14.7%), and longer inpatient stay (8.8 vs 4.3 d). They also had higher average (136.6 vs 119.6 mg/dL) and peak glucose levels (191.9 vs 153.1 mg/dL), as well as greater variability in glucose levels (92.1 vs 58.1 mg/dL). Multivariable logistic regression identified BMI (odds ratio [OR] = 1.13), diabetes mellitus (OR = 2.12), average glucose on the first postoperative day (OR = 1.24), peak postoperative glucose (OR = 1.31), and maximal daily glucose variation (OR = 1.32) as being significant independent predictors of postoperative surgical site infection. Postoperative hyperglycemia and poor postoperative glucose control are independent risk factors for surgical site infection following surgery for degenerative spine disease. These data suggest that, particularly among high-risk diabetic patients, strict perioperative glucose control may decrease the risk of SSI. Copyright © 2019 by the Congress of Neurological Surgeons.