Background: Several studies have suggested that intravenous insulin therapy for post-operative hyperglycemia improves outcomes after colorectal surgery. Despite the potential benefit, there is a reluctance to use this approach in patients without diabetes mellitus because of an unproven benefit and the potential for hypoglycemia. In this study, we examined whether sliding-scale insulin is sufficient to improve outcomes or if stricter glucose control is necessary. Patients and Methods: Of 1,064 consecutive colorectal surgery patients between August 2016 and December 2021, 478 patients without diabetes mellitus had an average of 6.4 ± 3.1 glucose samples taken within 48 hours after surgery. Sixty-six percent of patients with severe hyperglycemia (glucose ≥180 mg/dL) received sliding-scale insulin. Complication rates and effects of insulin were examined. Results: Severe hyperglycemia was associated with a higher total infection rate (p < 0.002), National Healthcare Safety Network-reported infections (NHSN; p < 0.026), total complications (p < 0.001), and length of stay (LOS; p < 0.000). Sliding-scale insulin did not lower the risk of infection or other complications. Hypoglycemia (glucose <70 mg/dL) occurred in 3.5% of patients, but was not related to insulin use, and was predictable with clinical variables: albumin (p < 0.032), operative duration (p < 0.012), and average post-operative glucose (p < 0.002; area under the curve [AUC], 0.86). Conclusions: Our data confirm that severe post-operative hyperglycemia in patients without diabetes mellitus after colorectal surgery is associated with complications. Sliding-scale insulin was safe but not effective. Treatment before severe hyperglycemia is reached, not after its occurrence, may be beneficial.