OBJECTIVES This study evaluated the contributions of obesity and changes in body mass index (BMI) in mid-life to long-term heart failure (HF) risk independent of cardiorespiratory fitness (CRF) levels. BACKGROUND Obesity and low CRF are well-established risk factors for HF. However, given the inverse association between CRF and obesity, the independent contributions of BMI toward HF risk are not fully understood. METHODS We included 19,485 participants from the Cooper Center Longitudinal Study who survived to receive Medicare coverage, from 1999 to 2009. CRF was estimated in metabolic equivalents (METS) according to Balke treadmill time. Associations of BMI and BMI change with HF hospitalization after age 65 were assessed by applying a proportional hazards recurrent events model to the failure time data. RESULTS After 127,110 person-years of follow-up, we observed 1,038 HF hospitalization events. Higher mid-life BMI was significantly associated with greater risk of HF hospitalization after adjusting for established HF risk factors (hazard ratio [HR]: 1.19; 95% confidence interval [CI]: 1.12 to 1.26 per 3 kg/m(2) higher BMI). This association was attenuated after adjusting for CRF (HR: 1.10; 95% CI: 1.03 to 1.17 per 3 kg/m(2) higher BMI). CRF accounted for 47% of the HF risk associated with BMI. BMI change was not significantly associated with risk of HF in older age after adjustment for CRF change. CONCLUSIONS Higher BMI-associated risk of HF is explained largely by differences in CRF levels. Furthermore, BMI change is not significantly associated with HF risk after adjusting for CRF changes. These findings highlight the importance of CRF in mediating BMI-associated HF risk. (J Am Coll Cardiol HF 2017;5:367-74) (C) 2017 by the American College of Cardiology Foundation.