Reduced kidney function is a risk factor for cardiovascular morbidity and mortality, and both heart failure (HF) and kidney failure incidences are increasing. This study therefore sought to determine the effect of decreased kidney function on HF incidence in a population-based study of middle-aged adults. From 1987 through 2002, 14,857 participants of the Atherosclerosis Risk in Communities (ARIC) study who were free of prevalent HF at baseline were followed for incident HF hospitalization or death (International Classification of Diseases, Ninth Revision/10th Revision 428/I50). Estimated GFR (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation, and kidney function was categorized as normal (eGFR > or =90 ml/min per 1.73 m(2); n = 7143), mildly reduced (eGFR 60 to 89 ml/min per 1.73 m(2); n = 7311), and moderately/severely reduced (eGFR <60 ml/min per 1.73 m(2); n = 403). Cox proportional hazards models were used to control for demographic and cardiovascular risk factors; analyses were stratified by the presence of coronary heart disease at baseline. During a mean follow-up of 13.2 yr, 1193 participants developed HF. The incidence of HF was three-fold higher for individuals with eGFR <60 ml/min per 1.73 m(2) compared to the reference group with eGFR > or =90 ml/min per 1.73 m(2) (18 versus 6 per 1000 person-years). The overall adjusted relative hazard of developing HF was 1.94 (1.49 to 2.53) for individuals with eGFR <60 ml/min per 1.73 m(2) compared to the reference group and was significantly increased for individuals with and without prevalent coronary heart disease at baseline. A substantially greater decline in kidney function occurred in individuals concomitant with HF hospitalization/death compared to those who did not develop HF. In summary, middle-aged adults with moderately/severely reduced kidney function are at high risk for developing HF.