Importance: Uninsured people uniquely rely on the emergency department (ED) for care as they are less likely to have access to lower-cost alternatives. Prior work has demonstrated that most uninsured patients are at risk of catastrophic health expenditure (CHE) after being hospitalized for life-saving care. The risk of CHE for a single treat-and-release ED visit that does not result in a hospitalization among uninsured patient encounters is currently unknown. Objective: To estimate the overall national risk of CHE among uninsured patients after a single treat-and-release ED visit from 2006 through 2017, and to characterize this risk across key traits. Design Setting and Population: This cross-sectional study is based on a nationally representative sample of hospital-based ED visits between 2006 and 2017 in the United States (US) from the Nationwide Emergency Department Sample (NEDS). It examined outpatient ED visits among uninsured patients. Main Outcomes and Measures: Risk of CHE for ED care defined as an ED charge that exceeds 40% of one's estimated annual post-subsistence income. Results: From 2006 to 2017, there were 41.7 million NEDS encounters that met inclusion criteria for this analysis, equating to a nationally weighted estimate of 184.6 million uninsured treat-and-release ED encounters over this period. The median ED charge for a single treat-and-release encounter grew from $842 in 2006 to $2033 by 2017. Approximately 1 in 5 uninsured patients (18% [95% CI, 18.0%-18.0%]) were at risk of CHE for a single treat-and-release ED visit over the study period. This estimated CHE risk increased from 13.6% (95% CI, 13.6%-13.6%) in 2006 to 22.6% (95% CI, 22.6%-22.7%) in 2017. Those living in the lowest income quartile faced a disproportionate share of this risk, with nearly 1 in 3 (28.5% [95% CI, 28.5%-28.6%]) facing CHE risk in 2017. In 2017, an estimated 3.2 million patient encounters nationally were at risk of CHE after a single treat-and-release ED visit. Conclusions and Relevance: This cross-sectional analysis from 2006 to 2017 of 184.6 million uninsured treat-and-release visits found that 1 in 5 uninsured patient encounters are at risk for CHE. This risk has grown over time. Future policies designed to improve access for unscheduled care must consider the unique role of the ED as the de facto safety net and ensure that uninsured patients are not at undue risk of financial harm for seeking care.