Objectives. We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infarction affected mortality during the subsequent 12 months of follow-up. Background. Despite significant improvements in acute coronary care, diabetic patients with acute myocardial infarction still have a high mortality rate. Methods. A total of 620 patients were studied : 306 randomized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for ≥3 months and 314 to conventional therapy. Results. The two groups were well matched for baseline characteristics. Blood glucose decreased from 15.4 ± 4.1 to 9.6 ± 3.3 mmol/liter (mean ± SD) in the infusion group during the 1st 24 h, and from 15.7 ± 4.2 to 11.7 ± 4.1 among control patients (p < 0.0001). After 1 year 57 subjects (18.6%) in the infusion group and 82 (26.1%) in the control group had died (relative mortality reduction 29%, p = 0.027). The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment (3-month mortality rate 6.5% in the infusion group vs. 13.5% in the control group [relative reduction 52%, p = 0.046] ; 1-year mortality rate 8.6% in the infusion group vs. 18.0% in the control group [relative reduction 52%, p = 0.020]). Conclusions. Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.