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The aims of this study were to determine differences in emergency department (ED) use by Native American (NA) children in rural and urban settings and identify factors associated with frequent ED visits.This cross-sectional, cohort study examined visits to 6 EDs: 2 rural, 2 midsize urban, and 2 large urban EDs from June 2011 to May 2012. Univariate and multiple regression analyses were conducted. Frequent ED visitors had more than 4 visits in the study period.We studied 8294 NA visits (5275 patients) and 44,503 white visits (33,945 patients). Rural EDs had a higher proportion of NA patients, those below 200% of the income poverty level, and those who traveled more than 10 miles from their residence to attend the ED (all P < 0.05) compared with midsize and urban EDs. Native American patients had a high proportion of mental health diagnoses compared with whites (4.9% vs 1.9%, P < 0.001). Frequent ED visitors had greater odds of NA race, age younger than 1 year, public insurance, female sex, residence within less than 5 miles from the ED, and chronic disease.Native American children seem to have greater challenges compared with whites obtaining care in rural areas. Native American children were more likely to be frequent ED visitors, despite having to travel farther from their residence to the ED. Native American children visiting rural and midsize urban EDs had a much higher prevalence of mental health problems than whites. Additional efforts to provide both medical and mental health services to rural NA are urgently needed.