Background Hypoglycemia is a known risk of intensive postoperative glucose control in patients undergoing cardiac operations. However, neither the consequences of hypoglycemia relative to hyperglycemia, nor the possible interaction effects, have been well described. We examined the effects of postoperative hypoglycemia, hyperglycemia, and their interaction on short-term morbidity and mortality. Methods Single-institution Society of Thoracic Surgeons (STS) database patient records from 2010 to 2014 were merged with clinical data, including blood glucose values measured in the intensive care unit (ICU). Exclusion criteria included fewer than three glucose measurements and absence of an STS predicted risk of morbidity or mortality score. Primary outcomes were operative mortality and composite major morbidity (permanent stroke, renal failure, prolonged ventilation, pneumonia, or myocardial infarction). Secondary outcomes included ICU and postoperative length of stay. Hypoglycemia was defined as below 70 mg/dL, and hyperglycemia as above 180 mg/dL. Simple and multivariable regression models were used to evaluate the outcomes. Results A total of 2,285 patient records met the selection criteria for analysis. The mean postoperative glucose level was 140.8 ± 18.8 mg/dL. Overall, 21.4% of patients experienced a hypoglycemic episode (n = 488), and 1.05% (n = 24) had a severe hypoglycemic episode (<40 mg/dL). The unadjusted odds ratio (UOR) for operative mortality for patients with any hypoglycemic episode compared with those without was 5.47 (95% confidence interval [CI] 3.14 to 9.54), and the UOR for major morbidity was 4.66 (95% CI 3.55 to 6.11). After adjustment for predicted risk of morbidity or mortality and other significant covariates, the adjusted odds (AOR) of operative mortality were significant for patients with any hypoglycemia (AOR 4.88, 95% CI 2.67 to 8.92) and patients with both events (AOR 8.29, 95% CI 1.83 to 37.5) but not hyperglycemia alone (AOR 1.62, 95% CI 0.56 to 4.69). The AOR of major morbidity for patients with both hypoglycemic and hyperglycemic events was 14.3 (95% CI 6.50 to 31.4). Conclusions Postoperative hypoglycemia is associated with both mortality and major morbidity after cardiac operations. The combination of both hyperglycemia and hypoglycemia represents a substantial increase in risk. Although it remains unclear whether hypoglycemia is a cause, an early warning sign, or a result of adverse events, this study suggests that hypoglycemia may be an important event in the postoperative period after cardiac operations.