OBJECTIVE: There is conflicting evidence regarding the benefit of intravenous insulin therapy on mortality following acute myocardial infarction (AMI). The goal of the current study was to determine whether improved glycemic control, achieved through an insulin/dextrose infusion with a variable rate of insulin, reduces mortality among hyperglycemic patients with AMI. RESEARCH DESIGN AND METHODS: Subjects suffering AMI with either known diabetes or without diabetes but blood glucose level (BGL) > or =7.8 mmol/l were randomized to receive insulin/dextrose infusion therapy for at least 24 h to maintain a BGL <10 mmol/l or conventional therapy. RESULTS: A total of 240 subjects were recruited. Insulin/dextrose infusion did not reduce mortality at the inpatient stage (4.8 vs. conventional 3.5%, P = 0.75), 3 months (7.1 vs 4.4%, P = 0.42), or 6 months (7.9 vs. 6.1%, P = 0.62). There was, however, a lower incidence of cardiac failure (12.7 vs. 22.8%, P = 0.04) and reinfarction within 3 months (2.4 vs. 6.1%, P = 0.05). When analyzed by mean BGL achieved during the first 24 h, mortality was lower among subjects with a mean BGL < or =8 mmol/l, compared with subjects with a mean BGL >8 mmol/l (2 vs. 11% at 6 months, P = 0.02). CONCLUSIONS: We did not find a reduction in mortality among patients who received insulin/dextrose infusion therapy. However, it remains possible that tight glycemic control with insulin therapy following AMI improves outcomes.