BACKGROUND The adverse impact of acute hyperglycemia is well documented but its specific effects on nondiabetic trauma patients are unclear. The purpose of this study was to analyze the differential impact of hyperglycemia on outcomes between diabetic and nondiabetic trauma inpatients. METHODS Adults admitted 2018 to 2019 to 46 Level I/II trauma centers with two or more blood glucose tests were analyzed. Diabetes status was determined from International Classification of Diseases—10th Rev.—Clinical Modification, trauma registry, and/or hemoglobin A1c greater than 6.5. Patients with and without one or more hyperglycemic result >180 mg/dL were compared. Logistic regression examined the effects of hyperglycemia and diabetes on outcomes, adjusting for age, sex, Injury Severity Score, and body mass index. RESULTS There were 95,764 patients: 54% male; mean age, 61 years; mean Injury Severity Score, 10; diabetic, 21%. Patients with hyperglycemia had higher mortality and worse outcomes compared with those without hyperglycemia. Nondiabetic hyperglycemic patients had the highest odds of mortality (diabetic: adjusted odds ratio, 3.11; 95% confidence interval, 2.8–3.5; nondiabetics: adjusted odds ratio, 7.5; 95% confidence interval, 6.8–8.4). Hyperglycemic nondiabetics experienced worse outcomes on every measure when compared with nonhyperglycemic nondiabetics, with higher rates of sepsis (1.1 vs. 0.1%, p