ObjectivePrevious retrospective studies have established a relationship between postoperative hypoglycemia and adverse outcomes following cardiac surgery, but none have accounted for the cause of hypoglycemia. MethodsA retrospective review was performed of cardiac surgery patients at a single institution between 2016 and 2021. Patients were categorized as hypoglycemic if they had one or more postoperative blood glucose measurement less than 70 mg/dL, and normoglycemic otherwise. Hypoglycemia was subcategorized as non-iatrogenic (underlying liver failure, adrenal insufficiency, sepsis, or shock) or iatrogenic (insulin infusion continued while nil-per-os or infusion protocol violated) via manual chart review. Baseline characteristics were compared between groups using Pearson’s chi-squared, ANOVA, and Kruskal-Wallis testing, and outcomes were compared using multivariable logistic regression. Results5,373 patients and 183,346 glucose measurements were included. Hypoglycemia occurred in 5% (267) of patients, of which 63% (169) were iatrogenic and 37% (98) were non-iatrogenic. In a multivariate analysis adjusting for age, sex, case urgency, pre-existing diabetes, and bypass time, both iatrogenic and non-iatrogenic hypoglycemia were associated with higher odds of renal failure, prolonged ventilation, and prolonged ICU length of stay relative to normoglycemia, but the magnitude was substantially lower in iatrogenic hypoglycemia. Non-iatrogenic hypoglycemic patients had 68.6 times greater odds of mortality relative to normoglycemic patients (OR 68.6, CI 39.5-119), but iatrogenic hypoglycemic patients had no increased odds of mortality (OR 1.45, CI 0.77-2.73). ConclusionsWhen excluding patients with conditions known to cause hypoglycemia from the analysis, the morbidity and mortality of iatrogenic hypoglycemia from tight postoperative glycemic control is dramatically attenuated.