BACKGROUND: Several experimental investigations have emphasized the favorable effects of insulin-like growth factor I (IGF-I) on left ventricular remodeling, partly through its antiapoptotic effects. Cross-sectional clinical studies have reported that low serum IGF-I levels in patients with heart failure correlate with cachexia and severity of ventricular dysfunction. It is unclear whether low serum IGF-I is a risk factor for heart failure. OBJECTIVE: To prospectively study the association between serum IGF-I level and the incidence of congestive heart failure. DESIGN: Community-based, prospective cohort study. SETTING: Framingham, Massachusetts. PARTICIPANTS: 717 elderly individuals (mean age, 78.4 years; 67% women) who did not have myocardial infarction and congestive heart failure at baseline. Measurement: Incidence of a first episode of congestive heart failure on follow-up. RESULTS: During follow-up (mean, 5.2 years), 56 participants (35 women) developed congestive heart failure. In multivariable Cox regression models adjusting for established risk factors at baseline, there was a 27% decrease in risk for heart failure for every 1 standard deviation increment in log IGF-I. Individuals with serum IGF-I level at or above the median value (140 microg/L) had half the risk for heart failure (hazard ratio, 0.49 [95% CI, 0.26 to 0.92]) of those with serum IGF-I levels below the median. These comparisons were maintained in analyses adjusting for the occurrence of a myocardial infarction on follow-up. CONCLUSIONS: In our prospective, community-based investigation, serum IGF-I level was inversely related to the risk for congestive heart failure in elderly people without a previous myocardial infarction. Additional investigations are warranted to confirm these findings.