In this study, the frequency of extended-spectrum b-lactamases (ESBL) and plasmid-mediated quinolone resistance (PMQR) mechanisms were investigated in 206 clinical isolates of third generation cephalosporin (3GC)-resistant Enterobacteriaceae in four hospitals in the Republic of Ireland. blaCTX-M-15 was the predominant ESBL gene. Of these 3GC resistant isolates, 54% were also resistant to ciprofloxacin. Investigation of the PMQR mechanisms revealed that the aac(69) Ib-cr gene predominated in fluoroquinolone-resistant (FQR) strains of Escherichia coli and Klebsiella pneumoniae, while the qnrA gene predominated in the FQR strains of Enterobacter. The blaCTX-M-15 gene was frequently identified with the aac(69)Ib-cr gene but was not always on the same plasmid. The prevalence of the blaCTX-M-15 gene appeared to be hospital-dependent. The epidemiology of both ESBL-producing and PMQR strains within the four hospitals indicated that their prevalence is not due to the spread of these resistance genes between isolates from different hospitals.