Previous studies have explored the ability of the Cardiac Infarction/Injury Score (CIIS) to identify individuals who are high-risk for cardiovascular disease (CVD) mortality. However, its prognostic significance among those without CVD in the United States general population has not been established. This analysis included 6,298 participants (mean age: 59 ± 13 years; 53% female; 51% non-whites) from the Third National Health and Nutrition Examination Survey (NHANES III), excluding participants with a history of CVD or electrocardiographic evidence of old myocardial infarction or ischemic ST depression at baseline. Subclinical myocardial injury was defined as CIIS ≥10. Mortality data were ascertained using the National Death Index. Cox proportional-hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for association between subclinical myocardial injury with CVD and all-cause mortalities. Subclinical myocardial injury was detected in 1,376 (22%) participants. A total of 1,928 deaths occurred during a median of 14 years follow-up, of which 765 (40%) were due to CVD. In a multivariable model adjusted for demographics, traditional CVD risk factors, and other medical comorbidities, subclinical myocardial injury was associated with an increased risk of CVD (HR=1.26, 95%CI=1.02, 1.56) and all-cause (HR=1.42, 95%CI=1.23, 1.63) mortalities. In conclusion, subclinical myocardial injury in persons without manifestations of CVD is associated with an increased risk of CVD and all-cause mortalities. These findings highlight the important role of CIIS to identify subclinical myocardial injury and its association with mortality among men and women in the United States.