OBJECTIVE Acute hyperglycemia is a powerful predictor of poor prognosis in acute myocardial infarction (AMI), particularly in patients without diabetes. This emphasizes the importance of an acute glycemic rise rather than glycemia level at admission alone. We investigated in AMI whether the combined evaluation of acute and chronic glycemic levels, as compared with admission glycemia alone, may have a better prognostic value. RESEARCH DESIGN AND METHODS We prospectively measured admission glycemia and estimated average chronic glucose levels (mg/dL) by the following formula: [(28.7 × glycosylated hemoglobin %) − 46.7], and calculated the acute-to-chronic (A/C) glycemic ratio in 1,553 consecutive AMI patients (mean ± SD age 67 ± 13 years). The primary end point was the combination of in-hospital mortality, acute pulmonary edema, and cardiogenic shock. RESULTS The primary end point rate increased in parallel with A/C glycemic ratio tertiles (5%, 8%, and 20%, respectively; P for trend <0.0001). A parallel increase was observed in troponin I peak value (15 ± 34 ng/mL, 34 ± 66 ng/mL, and 68 ± 131 ng/mL; P < 0.0001). At multivariable analysis, A/C glycemic ratio remained an independent predictor of the primary end point and of troponin I peak value, even after adjustment for major confounders. At reclassification analyses, A/C glycemic ratio showed the best prognostic power in predicting the primary end point as compared with glycemia at admission in the entire population (net reclassification improvement 12% [95% CI 4–20]; P = 0.003) and, particularly, in patients with diabetes (27% [95% CI 14–40]; P < 0.0001). CONCLUSIONS In AMI patients with diabetes, A/C glycemic ratio is a better predictor of in-hospital morbidity and mortality than glycemia at admission.