Renal function predicts mortality after acute myocardial infarction (AMI), but it is unknown whether the prognostic importance of renal function persists over time. This study examined how the association between renal function and mortality changed in the 10 yr after AMI in a cohort of patients. In 118,753 patients (age >/=65 yr) from the Cooperative Cardiovascular Project, mean Cockcroft-Gault creatinine clearance was 55 +/- 24 ml/min and estimated GFR was 57 +/- 21 ml/min per 1.73 m(2) at baseline. By 10 yr, 68% of patients had died. Compared with normal renal function, even mild renal impairment increased the 10-yr risk for mortality risk by 10%. Severe renal impairment more than doubled the risk for mortality at 1 yr, and this increased risk persisted at both 5 and 10 yr. At 1 yr, the contribution of creatinine clearance to mortality risk rivaled traditional factors such as BP and systolic function; by 10 yr, creatinine clearance surpassed these other risk factors, rivaled only by patient age. Associations with estimated GFR demonstrated similar trends. In conclusion, renal function in hospitalized patients with AMI is an important and consistent predictor of mortality for up to 10 yr.