This cross-sectional study of US nationwide emergency department data examines the incidence, common injury mechanisms, and economic burden of ocular trauma open globe injuries in the United States. Importance Open globe injuries can lead to substantial visual morbidity and lifelong sequelae. Interventions to reduce the burden of open globe injuries in the United States require a better understanding of these injuries through well-designed epidemiologic investigations. Objective To examine the incidence, common injury mechanisms, and economic burden of open globe injuries in the United States. Design, Setting, and Participants This retrospective, cross-sectional study of US nationwide emergency department (ED) data assessed all ED visits of patients with a primary diagnosis of open globe injury in the Nationwide Emergency Department Sample (NEDS) from January 1, 2006, to December 31, 2014. Data analysis was performed from August 29, 2018, to November 11, 2019. Main Outcomes and Measures Annual incidence of open globe injuries by age, sex, mechanism of injury, and concomitant diagnosis, as well as median charges associated with open globe injuries and variables associated with hospitalization. Results A total of 124989 ED visits for open globe injuries were assessed, with an incidence of 4.49 per 100000 population in the United States from 2006 to 2014 (mean [SD] age of study participants, 37.7 [22.5] years; 94078 [75.3%] male). The incidence was highest in 2006 (5.88 per 100000 population) and decreased by 0.3% per month between 2006 and 2014 (incidence rate ratio, 0.99; 95% CI, 0.99-0.99; P < .001). Open globe injuries occurred in 37060 individuals (30.6%) of low socioeconomic status. The most common injury mechanism was being struck by or against an object or person (40119 of all 124 989 injury mechanisms [32.1%]). Open globe injuries associated with falls increased 6.6% between 2006-2010 and 2011-2015 (95% CI, 1.04-1.08; P < .001) and were the most common injury mechanism in individuals older than 70 years. The total cost associated with open globe injuries was $793 million. The cost of ED visits increased from $865 during 2006-2010 to $1557 during 2011-2015. Inpatient costs similarly increased from $21527 during 2006-2010 to $30243 during 2011-2015. Conclusions and Relevance The incidence of open globe injuries in the United States decreased from 2006 to 2014. Although the data are from 5 to 13 years ago, these findings appear to provide valuable information for targeting preventive measures toward individuals at highest risk; targeting young men with lower socioeconomic status and individuals 70 years or older at an increased risk of falls may help lower the incidence of open globe injuries. Question What were the population-based characteristics of open globe injuries in the United States from 2006 to 2014 from the Nationwide Emergency Department Sample? Findings This cross-sectional study of 124989 emergency department visits for open globe injuries found that the incidence of open globe injuries was 4.49 per 100000 population, accounting for $793 million in total charges. Males and individuals with a low socioeconomic status were at increased risk, and the incidence of open globe injuries associated with falls increased during the study period. Meanings These results suggest preventive efforts for open globe injuries should target males, individuals at risk for falls, and those from a low socioeconomic background.