OBJECTIVE: Patients with acute myocardial infarction (MI) have increased risk of developing type 2 diabetes mellitus (T2DM). Adiponectin is an insulin-sensitizing hormone produced in adipose tissue, directly suppressing hepatic gluconeogenesis, stimulating fatty acid oxidation and glucose uptake in skeletal muscle and insulin secretion. In healthy humans, low plasma adiponectin levels associate with increased risk of T2DM; however, the relationship between adiponectin and T2DM in patients with MI has never been investigated. RESEARCH DESIGN AND METHODS: We prospectively included 666 patients with ST-segment elevation MI, without diabetes, treated with percutaneous coronary intervention, from September 2006 to December 2008 at a tertiary cardiac center. Blood samples were drawn before intervention, and total plasma adiponectin was measured in all samples. During follow-up (median 5.7 years [interquartile range 5.3-6.1]) 6% (n = 38) developed T2DM. Risk of T2DM was analyzed using a competing risk analysis. RESULTS: Low adiponectin levels were associated with increased risk of T2DM (P < 0.001). Even after adjustment for confounding risk factors (age, sex, hypertension, hypercholesterolemia, current smoking, previous MI, BMI, blood glucose, total cholesterol, HDL, LDL, triglyceride, estimated glomerular filtration rate, C-reactive protein, peak troponin I, and proatrial natriuretic peptide), low adiponectin levels remained an independent predictor of T2DM (hazard ratio [HR] 5.8 [2.3-15.0]; P < 0.001). Importantly, plasma adiponectin added to the predictive value of blood glucose, with the combination of high blood glucose and low plasma adiponectin, vastly increasing the risk of developing T2DM (HR 9.6 [3.7-25.3]; P < 0.001). CONCLUSIONS: Low plasma adiponectin levels are independently associated with increased risk of T2DM in patients with MI and added significantly to the predictive value of blood glucose.