Background. We conducted this case-control study to determine the risk factors and treatment outcome of infections due to carbapenem resistant Enterobacteriaceae in our institution. Methods. This is a matched case-control study of patients with infection due to carbapenem resistant Enterobacteriaceae (CRE) and carbapenem susceptible Enterobacteriaceae (CSE), from Riyadh, Saudi Arabia, between March 2012 and December 2013. Results. During this period, 29 cases and 58 controls were studied. The mean ages of the cases (55.4 years) and controls (54.7 years) were similar (p = 0.065). Cases had higher mean Charlson comorbidity index (CCI) (3.1) than controls (1.9), p = 0.026. Several factors contributed to infection among the studied population. Prior uses of piperacillin-tazobactam, a carbapenem, a quinolone, and metronidazole were significantly associated with CRE infections. Nine of the cases died compared with 7 of the controls, p = 0.031. Mortality was associated with advanced age, the presence of comorbidities, ICU stay, and receipt of invasive procedures. Conclusions. Infections due to CRE resulted in a significantly increased mortality. Combination antibiotic therapy was associated with reduced mortality. Properly designed randomized controlled studies are required to better characterize these findings.