© 2017 The Authors. Background-The National Death Index (NDI) is widely used to detect coronary heart disease (CHD) and cardiovascular disease (CVD) deaths, but its reliability has not been examined recently. Methods and Results-We compared CHD and CVD deaths detected by NDI with expert adjudication of 4010 deaths that occurred between 2003 and 2013 among participants in the REGARDS (REasons for Geographic And Racial Differences in Stroke) cohort of black and white adults in the United States. NDI derived CHD mortality had sensitivity 53.6%, specificity 90.3%, positive predictive value 54.2%, and negative predictive value 90.1%. NDI-derived CVD mortality had sensitivity 73.4%, specificity 84.5%, positive predictive value 70.6%, and negative predictive value 86.2%. Among NDI-derived CHD and CVD deaths, older age (odds ratios, 1.06 and 1.04 per 1-year increase) was associated with a higher probability of disagreement with the adjudicated cause of death, whereas among REGARDS adjudicated CHD and CVD deaths a history of CHD or CVD was associated with a lower probability of disagreement with the NDI-derived causes of death (odds ratios, 0.59 and 0.67, respectively). Conclusions-The modest accuracy and differential performance of NDI-derived cause of death may impact CHD and CVD mortality statistics.