Context: Hyperglycemia in hospitalized patients is associated with increased morbidity and mortality. Objective: We examined whether critical illness is more strongly associated with relative or absolute hyperglycemia. Design: The study was an observational cohort study. Patients and Setting: A total of 2290 patients acutely admitted to a tertiary hospital. MainOutcomeMeasure: The relative hyperglycemia (stress hyperglycemia ratio [SHR])wasdefined as admission glucose divided by estimated average glucose derived from glycosylated hemoglobin. The relationships between glucose and SHR with critical illness (in-hospital death or critical care) were examined. Results: In univariable analyses, SHR (odds ratio, 1.23 per 0.1 increment [95% confidence interval, 1.18-1.28]; P<.001) and glucose (odds ratio, 1.18 per mmol/L [1.13-1.23]; P<.001) were associated with critical illness. In multivariable analysis, the association was maintained for SHR (odds ratio, 1.20 per 0.1 increment [1.13-1.28]; P < .001), but not glucose (odds ratio, 1.03 per mmol/L [0.97-1.11]; P = .31). Background hyperglycemia affected the relationship between glucose (P = .002) and critical illness, but not SHR (P=.35) and critical illness. In patients with admission glucose ≤10 mmol/L, the odds ratio for critical illness was higher in the fourth (2.4 [1.4-4.2]; P=.001) and fifth (3.9 [2.3- 6.8]; P < .001) SHR quintiles than in the lowest SHR quintile. Conclusions: SHR controls for background glycemia and is a better biomarker of critical illness than absolute hyperglycemia. SHR identifies patients with relative hyperglycemia at risk of critical illness. Future studies should explore whether basing glucose-lowering therapy on relative, rather than absolute, hyperglycemia improvesoutcomesin hospitalized patients.