Surveillance studies typically fail to provide sufficient information on how susceptibility rates differ among institutions and within patient age groups. Furthermore, antimicrobial resistance in context with resistance to other antimicrobial classes may help to understand resistance trends and may be useful for implementing control initiatives. This study used The Surveillance Network-USA (TSN-USA) and the Tracking Resistance in the United States Today (TRUST) surveillance data (2003-2005) to analyze multidrug-resistant (MDR) Escherichia coli at 229 institutions across the United States. Institutions with a higher prevalence of E coli resistant to multiple nonfluoroquinolone agents were associated with lower fluoroquinolone susceptibility. The prevalence of fluoroquinolone and multidrug resistance was also associated with increased patient age and locations such as long-term care facilities. Institutions attempting to understand and control E coli resistance to fluoroquinolones should carefully examine the patient population and prevalence of resistance to other agents.