The recent increase in multidrug-resistant (MDR) Escherichia coli infections is not well described in children. We determined the risk factors and outcomes of extraintestinal E. coli infections in children in our region. We conducted a retrospective cohort study of children <= 18 years in Olmsted County, MN, USA, between January 1, 2012 and December 31, 2012. MDR isolates were defined as resistant to >= 3 antibiotic classes. A total of 368 children each contributed 1 isolate. Isolates were predominantly community-associated (82%) and from urine (90%), and outpatients (86%); 46 (13%) isolates were MDR. In multivariable analysis, genitourinary (GU) tract anomaly (OR 2.42, 95% CI 1.03-5.68), invasive devices (OR 3.48, 95% CI 1.37-8.83) and antibiotic use at presentation (OR 2.62, 95% CI 1.06-6.47) were associated with MDR E. coli. Children with MDR infections were more likely to have a complex infection (35% vs. 17%, P = 0.026), less likely to receive effective empiric antibiotics (47% vs. 74%, P < 0.001), had longer time to receipt of effective antibiotics (median 19.2 vs. 0.6 h, P < 0.001), and longer hospitalization (median 10 vs. 4 days, P = 0.029) than children with non-MDR infections. Pediatric MDR E. coli infection was associated with GU tract anomaly, invasive devices, antibiotic use, delays in effective therapy and longer hospitalization.