The authors estimated the generalized impact fraction (GIF) for heart failure (HF) related to obesity, representing the proportion of incident HF events that could be prevented from reductions in obesity and/or overweight. The Atherosclerosis Risk in Communities Study is a biracial population-based cohort study of persons aged 45-64 years from 4 US communities with a median 14 years of follow-up (1987-2003) for incident, hospitalized, or fatal HF. Body mass index (BMI; weight (kg)/height (m)(2)) was measured at baseline (1987-1989) and categorized as normal weight (BMI <25), overweight (BMI 25-29.9), or obese (BMI ≥30). After exclusion of prevalent HF, missing BMI, and poorly represented racial groups, the sample size was 14,642. The GIF and attributable fraction were calculated using a case-load weighted-sum method. A 95% distribution of the GIF was estimated from bootstrapped data sets. A 30% hypothetical reduction in obesity/overweight would potentially prevent 8.5% (95% simulation interval: 6.1, 10.7) of incident HF events. The attributable fraction, which assumes complete elimination of obesity/overweight, was 28% (95% simulation interval: 20, 36)-approximately 3 times larger than the most optimistic GIF calculated here. Investigators studying exposures that are unlikely to be eradicated given current prevention efforts, such as obesity, should consider estimating the GIF to avoid overestimates of population impact.