To analyze the clinical features and the pathogenic constituent of patients with pyogenic liver abscess (PLA), and to find the risk factors of the multidrug resistance (MDR) pyogenic liver abscess (MDR-PLA) for effective therapy in the PLA patients. We reviewed the PLA patients with antibiotics susceptibility test, who admitted to Xiangya Hospital of Central South University from Jan. 2010 to Dec. 2019. A total of 157 cases were divided into 2 groups: an MDR-PLA group (n=52) and a non-MDR-PLA group (n=107). The clinical data such as age, symptoms, laboratory and imaging data, and etiological test especially drug sensitivity test of the 2 groups were collected. Logistic regression analysis was performed for the risk factors of MDR-PLA. Anorexia (90.38%) and abdominal pain (63.46%) were more common in the MDR-PLA group than those in the non-MDR-PLA group (P<0.05). The proportions of patients with hepatolithiasis (34.62%) and biliary tract operation (38.62%) were higher in the MDR-PLA group than those in the non-MDR-PLA group (P<0.05). Klebsiellapneumoniae (59.94%) was the most common pathogen, which was sensitive to most of the antibiotics, while Escherichia coli and Enterococcus had lower drug sensitivity than Klebsiella lebsiella pneumoniae. The MDR-Enterococcus was 6.5 times of non-MDR-Enterococcus. And the multidrug resistance Klebsiella pneumoniae was 3.4 times of non-MDR-Klebsiella pneumoniae. Logistic regression analysis showed that hepatolithiasis (OR=4.895, 95% CI 1.455 to 16.463, P=0.001) and biliary tract operation (OR=3.860, 95% CI 1.156 to 12.889, P=0.004) were the risk factors for the MDR-PLA patients. The PLA patients with hepatolithiasis and billary tract operation history and the pathogenic bacterium of Escherichia coli and Enterococcus bacteria should be alerted for MDR bacterial infection.