The increasing health burden and mortality from hepatitis B virus (HBV) and hepatitis C virus (HCV) in the United States are underappreciated. To examine mortality from HBV; HCV; and, for comparison, HIV. Analysis of U.S. multiple-cause mortality data from 1999 to 2007 from the National Center for Health Statistics. All U.S. states and the District of Columbia. Approximately 22 million decedents. Age-adjusted mortality rates from HBV, HCV, and HIV. Logistic regression analyses of 2007 data generated 4 independent models per outcome (HCV- or HBV-related deaths) that each included 1 of 4 comorbid conditions and all sociodemographic characteristics. Between 1999 and 2007, recorded deaths from HCV [corrected] increased significantly to 15,106, whereas deaths from HIV declined to 12,734 by 2007. Factors associated with HCV-related deaths included chronic liver disease, HBV co-infection, alcohol-related conditions, minority status, and HIV co-infection. Factors that increased odds of HBV-related death included chronic liver disease, HCV co-infection, Asian or Pacific Islander descent, HIV co-infection, and alcohol-related conditions. Most deaths from HBV and HCV occurred in middle-aged persons. A person other than the primary physician of the decedent frequently completed the death certificate, and HCV and HBV often were not detected and thus not reported as causes of death. By 2007, HCV had superseded HIV as a cause of death in the United States, and deaths from HCV and HBV disproportionately occurred in middle-aged persons. To achieve decreases in mortality similar to those seen with HIV requires new policy initiatives to detect patients with chronic hepatitis and link them to care and treatment. Centers for Disease Control and Prevention.