Previous studies have reported that acute hyperglycemia is associated with high mortality after acute myocardial infarction (AMI). However, optimal plasma glucose level may be different between diabetic and nondiabetic patients. The purpose of this study was to assess the relation between admission glucose and in-hospital mortality after AMI in patients with and without diabetes. This study consisted of 3,750 patients who were admitted to the 35 hospitals participating to the Japanese Acute Coronary Syndrome Study (JACSS) group within 48 hours after the onset of AMI. Plasma glucose was measured at the time of hospital admission. In patients without a history of diabetes, there was a linear relation between admission glucose and in-hospital mortality. Nondiabetic patients with a glucose level <6 mmol/L had the lowest mortality (2.5%). As admission glucose increased by 1 mmol/L, mortality increased by 17% (13% to 21%, p <0.001). In patients with a history of diabetes, however, there was a U-shape relation between glucose and mortality. Diabetic patients with glucose 9 to 10 mmol/L had the lowest mortality (1.9%); not only severe hyperglycemia (glucose > or =11 mmol/L, 9.1%, p <0.001) but also euglycemia (glucose <7 mmol/L, 9.4%, p = 0.009) were associated with higher mortality compared to moderate hyperglycemia (glucose 9 to 11 mmol/L, 3.2%). Diabetic patients with admission glucose 9 to 10 mmol/L had the lowest mortality, whereas lower glucose was better in nondiabetic patients. In conclusion, optimal glucose level on admission may be different between diabetic and nondiabetic patients with AMI.