A large number of nonfatal injuries are treated in U.S. emergency departments (EDs) every year. CDC's National Center for Health Statistics estimates that approximately 29% of all ED visits in 2010 were for injuries. To assess the economic impact of ED-treated injuries, CDC examined injury data from the National Electronic Injury Surveillance System--All Injury Program (NEISS-AIP) for 2013, as well as injury-related lifetime medical and work-loss costs from the Web-Based Injury Statistics Query and Reporting System (WISQARS). NEISS-AIP collects data from a nationally representative sample of EDs, using specific guidelines for recording the primary diagnosis and mechanism of injury. Number of injuries, crude- and age-specific injury rates, and total lifetime work-loss costs and medical costs were calculated for ED-treated injuries, stratified by sex, age groups, and intent and mechanism of injury. ED-treated injuries were further classified as those that were subsequently hospitalized or treated and released. The rate of hospitalized injuries was 950.8 per 100,000, and the rate of treated and released injuries was 8,549.8 per 100,000. Combined medical and work-loss costs for all ED-treated injuries (both hospitalized and treated and released) were $456.9 billion, or approximately 68% of the total costs of $671 billion associated with all fatal and ED-treated injuries. The substantial economic burden associated with nonfatal injuries underscores the need for effective prevention strategies.