A case-control study was performed with the objective of analysing risk factors and clinical features of infections caused by plasmid-mediated AmpC beta-lactamase (plasmid AmpC)-producing Enterobacteriaceae. All patients infected with plasmid AmpC-producing Enterobacteriaceae in two tertiary care hospitals from December 2006 to August 2007 were included. Plasmid AmpC enzymes were characterised by isoelectric focusing, enzyme inhibition assay and enzyme-specific polymerase chain reaction. A total of 30 patients (20 with Klebsiella pneumoniae and 10 with Escherichia coli) were recruited prospectively. CMY-2 and DHA-1 were the most common plasmid AmpC in E. coli and K. pneumoniae, respectively. An independent risk factor for infection with plasmid AmpC-producing Enterobacteriaceae was the use of an oxyimino-cephalosporin within 1 month of plasmid AmpC infection [adjusted odds ratio (aOR), 10.8, 95% confidence interval (CI), 1.6-75.4; P=0.016], with the use of a urinary catheter showing borderline significance (aOR, 6, 95% CI 0.93-38.4; P=0.06). An independent risk factor for treatment failure at 72 h was infection due to plasmid AmpC-producing Enterobacteriaceae (aOR, 9.78, 95% CI 1.34-71.17; P=0.02). These results suggest that infections caused by plasmid AmpC-producing isolates significantly increase treatment failure at 72 h and that prior use of an oxyimino-cephalosporin is a risk factor for infections caused by plasmid AmpC-producing Enterobacteriaceae.