In vitro, ciprofloxacin can select for dual resistance to fluoroquinolones and imipenem in Pseudomonas aeruginosa via a mutation in the regulatory gene, mexT, which downregulates OprD and upregulates MexEF-OprN. We performed a nested case-control study of patients in two medical intensive care units participating in an observational cohort study. Patients colonized or infected with P. aeruginosa resistant to both ciprofloxacin and imipenem (cases) were compared to controls. The presence of OprD and OprN from cases was evaluated by Western blot. In total, 44 cases were compared to 132 controls. Imipenem exposure [adjusted odds ratio (AOR) = 11.4, p = 0.044] was significantly associated with case status, but fluoroquinolone use was not (AOR = 1.0, p = 0.998). Neither OprD nor OprN were detected in any isolate. Fluoroquinolone use was not a risk factor for acquisitions of dually resistant P. aeruginosa. The absence of OprN in these isolates suggests that dual resistance is not due to mexT mutations.