OBJECTIVETo evaluate risk factors for and molecular characteristics of community-onset extended-spectrum cephalosporin-resistant (ESC-R) Enterobacteriaceae (EB) urinary tract infections (UTIs) in a US health system.DESIGNCase-control study.PARTICIPANTSAll patients presenting to the emergency department or outpatient practices with EB UTIs from December 21, 2010, through April 22, 2013, were included. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched 1:1 on study year.METHODSRisk factors for ESC-R EB UTI were assessed using multivariable conditional logistic regression. A subset of case isolates was evaluated for extended-spectrum beta-lactamases.RESULTSA total of 302 patients with community-onset EB UTI were included, of which 151 were cases. On multivariable analysis, risk factors for ESC-R EB UTI included trimethoprim-sulfamethoxazole use in the prior 6 months (odds ratio, 2.40 [95% CI, 1.22–4.70];P=.01), older age (1.03 [1.01–1.04];P<.001), diabetes (2.91 [1.32–6.41];P=.008), and presentation to the emergency department ( 2.42 [1.31–4.46];P=.005). The prevalence of extended-spectrum beta-lactamases among 120 case isolates was 52% CTX-M, 29% TEM, 20% OXA, and 13% SHV. The prevalence of AmpC was 25%. Pulsed-field gel electrophoresis of the CTX-MEscherichia coliisolates showed no distinct clusters.CONCLUSIONSUse of trimethoprim-sulfamethoxazole, older age, diabetes, and presentation to the emergency department were associated with community-onset ESC-R EB UTI. There was a high prevalence of CTX-M among our community isolates. Further studies are needed to determine strategies to limit emergence of these organisms in the community.Infect Control Hosp Epidemiol2016;1433–1439