Elevated HbA1c is associated with increased surgical site infections (SSI) in neurosurgical patients. How blood glucose control in the early post-operative period relates to SSI is incompletely understood. We hypothesized that poor early post-operative blood glucose control would be associated with SSI. Data from patients undergoing neurosurgical procedures at University of Missouri Hospital was retrospectively collected. Post-operative blood glucose for 72 h after surgery was assessed and categorized by levels of hyperglycemia; those with glucose ≥200 mg/dl were classified as poorly controlled. Patients with SSI were compared to patients without SSI using Chi-Square test with Fisher's exact test when appropriate. Of 500 patients having surgery, 300 had at least one post-operative blood glucose measurement. Of those 300 patients, 19 (6.33%) developed SSI. Patients with SSI had significantly higher mean post-operative blood glucose levels (p = 0.0081) and a greater mean number of point-of-care glucose level measurements >150 mg/dL (p = 0.0434). Pre-operative HbA1c and SSI were not associated (p = 0.0867). SSI was associated with pre-operative glucocorticoid use (p = 0.03), longer operative procedure (p = 0.0072), and required use of post-operative insulin drip (p = 0.047). Incidence of other wound complications (cellulitis, deep infection, dehiscence) increased with increase in post-operative blood glucose levels to >225 mg/dL. Post-operative hyperglycemia is associated with SSI after neurosurgical procedures, emphasizing the importance addressing blood glucose control after surgery.