We analyzed US multiple cause-of-death data for 2003-2006 for demographic and clinical determinants for autopsy in unexplained deaths possibly resulting from infectious causes. For 96,242 deaths, the definition for unexplained death was met and autopsy status was recorded. Most decedents were male, 40-49 years of age, and white. To identify factors associated with unexplained death, we used data from Arizona records. Multivariate analysis of Arizona records suggested that decedents of races other than white and black and decedents who had clinicopathologic syndromes in the cardiovascular, sepsis/shock, and multisyndrome categories recorded on the death certificate were least likely to have undergone autopsy; children with unexplained death were the most likely to have undergone autopsy. Improved understanding of unexplained deaths can provide opportunities for further studies, strengthen collaboration between investigators of unexplained deaths, and improve knowledge and awareness of infectious diseases of public health concern.