Background: We evaluated the specific association between a fitness-fatness index (FFI) and all-cause mortality among a national sample of US adults with coronary artery disease, congestive heart failure, or myocardial infarction. This FFI has recently emerged in the literature as a novel index of health. Hypothesis: We hypothesize that FFI will be inversely associated with mortality risk. Methods: The FFI was calculated as cardiorespiratory fitness divided by waist-to-height ratio. Data from the 1999-2006 National Health and Nutrition Examination Survey were used to identify 1206 participants, ages 20 to 85. Person-months of follow-up were calculated from the date of interview until date of death or censoring on December 31, 2011, whichever came first. Results: In a Cox proportional hazards model, for every 1-FFI-unit increase, participants had a 6% reduced all-cause mortality rate (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.910.97, P = 0.001; N = 1206). Results were similar among those diagnosed with coronary artery disease (HR: 0.94, 95% CI: 0.90-0.98, P = 0.007), congestive heart failure (HR: 0.95, 95% CI: 0.91-0.99, P = 0.02), or myocardial infarction (HR: 0.96, 95% CI: 0.92-0.99, P = 0.04). When examined in isolation, only fitness (and not fatness) was linked with survival benefits. Conclusions: In this national sample, increased FFI was associated with reduced risk of all cause mortality; this association was driven by the beneficial effects of fitness. This underscores the importance of tailored cardiac rehabilitation programs designed to promote fitness, in particular, among cardiac populations.