Introduction: Pyogenic liver abscess is associated with significant morbidity and mortality. The overall case fatality rate for pyogenic liver abscess is 5.6%. The incidence of pyogenic liver abscess in North America has steadily increased over the past decade, is currently estimated to be 2.3 cases per 100,000, and is higher among men than women. Case Report: A 51-year-old white female with past medical history of hypertension presented to the primary care clinic with a 2-week history of abdominal pain and generalized malaise. She denied any history of recent travel, intravenous drug abuse, alcoholism, recent surgical or endoscopic procedures. She was noted to be febrile, and abdominal examination revealed right upper quadrant tenderness. She was then transferred to the emergency department, where laboratory work-up revealed an elevated white blood cell count of 18 x 109 cells. Contrast enhanced computerized tomographic (CECT) scan of the abdomen showed multiple peripherally enhancing lesions in both lobes of the liver, suggestive of multiple liver abscesses. The largest collection measuring 7 cm in the right posterior lobe was drained using a CT guided pig tail catheter insertion. Gram stain and culture of the aspirate grew Enterobacter cloacae. She was treated with intravenous piperacillin-tazobactam for 4 weeks, followed by oral levofloxacin and metronidazole for another 4 weeks. Follow-up evaluation at 6 weeks after treatment completion showed complete radiographic resolution. Discussion:Enterobacter cloacae is a gram-negative, facultative anaerobic, rod-shape bacteria found as a normal gut flora in many human beings. In the U.S., the more commonly identifiable organisms in patients with pyogenic liver abscess are E.coli and Streptococcus species. However, Asian and African countries report a higher prevalence of parasitic and Klebsiella infections. Enterobacter cloacae infections are commonly seen in patients with an underlying hepato-biliary or pancreatic disease, recent surgical procedure, or with an underlying malignancy, especially colon cancer. To our knowledge, this is the first reported case of Enterobacter cloacae infection causing a clinically significant pyogenic liver abscess in a patient with no identifiable risk factors. The exact mechanism of the spread of this organism is uncertain, but spontaneous bacterial translocation seems to be the most likely explanation. This is particularly worrisome, as significant antimicrobial resistance exists within this group of species. Our patient was treated with a CT-guided drainage in combination with prolonged antibiotics in a relatively large size abscess (>5 cm) with good outcome and avoiding a surgical intervention.