PURPOSE: Emergency department (ED) patients receive medications that place them at risk for adverse events, including drug-induced prolongation of the QT interval, which can lead to Torsade de Pointes and sudden cardiac death. We report the frequency of prescription and co-prescription of QT-prolonging medications in US EDs and factors associated with high-risk prescribing practices. METHODS: We analyzed the ED component of the National Hospital Ambulatory Medical Care Survey for 1995 through 2009. Yearly rates of visits involving the prescription of QT-prolonging medications were determined. Multivariate regression analyses identified factors associated with the prescription of two or more QT-prolonging medications. RESULTS: Approximately 16.5 million visits annually (15.0%) involved prescription of a QT-prolonging drug, with 1.7 million (1.6%) involving multiple prescriptions. Visits associated with QT-prolonging drugs more than doubled over the study period (10.4% to 22.2%). Diphenhydramine, azithromycin, and ondansetron were most frequently implicated (46.1% of cases). The most commonly prescribed combination was diphenhydramine and famotidine, both QT-prolonging medications available over-the-counter. Female gender and older age were associated with co-prescription of QT-prolonging medications. The rate of EKG screening among visits associated with QT-prolonging drug combinations was low (20.9%), but more common than among visits without a QT-prolonging drug (OR 1.3; 95% CI 1.2-1.5). CONCLUSION: Use of QT-prolonging medications is increasing in EDs nationally. A small number of agents account for a large proportion of these visits and may represent an area for targeted screening or monitoring interventions in the ED.