Renal dysfunction is an independent risk factor for cardiovascular (cv) disease and its associated complications. Diabetes mellitus (dm) is a common cause of renal dysfunction. Whether the presence or absence of dm modifies the relation between renal dysfunction and cv disease is unclear. The valiant trial identified 14,527 patients with acute myocardial infarction complicated by either clinical or radiologic signs of heart failure and/or left ventricular dysfunction for whom baseline creatinine was measured. Patients were randomly assigned to receive captopril, valsartan, or both. Glomerular filtration rate (gfr) was estimated using the 4-component modification of diet in renal disease equation. Using multivariable cox proportional modeling, the relation of overall mortality and composite cardiovascular events with estimated gfr (egfr) between patients with and without dm was compared. Mean egfrs were 66.8 +/- 22.0 and 71.2 +/- 21.0 ml/min/1.73 m2 for patients with (n = 3,358) and without dm (n = 11,169), respectively. The likelihood of experiencing death or the composite end point was higher in patients with than without dm for each level of renal function. the augmentation in risk of cv events based on reduced renal function was similar between groups. Each decrease in egfr by 10 units was associated with hazards of 1.09 (95% confidence interval 1.06 to 1.12, p <0.001) in patients with dm and 1.08 (95% confidence interval 1.06 to 1.10, p <0.001) in patients without dm for risk of fatal and nonfatal cv outcomes independent of treatment assignment. In conclusion, although dm is associated with higher risk of renal dysfunction and adverse cv outcomes, patients without dm had a relation between renal function and cv risk similar to that for patients with dm after high-risk acute myocardial infarction.