Nowadays, pyogenic liver abscess (PLA) is still a common and severe intra-abdominal infection, and Klebsiella pneumoniae had emerged as the most common pathogenic bacteria worldwide in the past ten years. Our study aims to achieve an early pathogenic diagnosis and rational therapy modality for Klebsiella pneumoniae liver abscess (KLA) through clinical data analysis. A total of 197 inpatients in Zhongshan Hospital, Shanghai, diagnosed as having liver abscess between March 2001 and September 2009 were enrolled. Patients with monomicrobial infection were divided into two groups: patients with K. pneumoniae liver abscess (KLA group, n=106) and those with non-Klebsiella pneumoniae liver abscess (NKLA group, n=56). A retrospective analysis was made between these two groups on the aspects of underlying diseases, clinical characteristics, laboratory data, culture results, and imaging findings. To evaluate the effects of different medical interventions, monomicrobial KLA patients were further divided into four subgroups (percutaneous liver aspiration, aspiration plus antibiotics flushing, aspiration plus retained catheter, and aspiration plus antibiotics flushing and retained catheter), and corresponding therapeutic effects were analyzed. KLA was more likely to occur in patients with coexisting diseases such as diabetes mellitus (53.77% vs 25.00%, P=0.001) and hepatic adipose infiltration (16.04% vs 5.36%, P=0.029). Compared to NKLA group, clinical characteristics including abdominal pain (40.57% vs 57.14%, P=0.044), hypodynamia (19.81% vs 46.43%, P=0.001), and hepatomegaly (4.72% vs 14.29%, P=0.033) were much milder, but with a higher fasting blood glucose level (7.84?±?0.36 vs 5.76?±?0.30, P=0.001) on admission in KLA group. In addition, KLA abscess often appeared singly in the right lobe of the liver with gas forming nature (32.88% vs 13.51%, P=0.039), unsmooth rim (71.23% vs 40.54%, P=0.002), and dynamic septum enhancement (41.10% vs 16.22%, P=0.009). Compared to mono aspiration subgroup, additional antibiotic flushing could not further improve clinical outcomes of KLA patients (P>0.05); however, the retained catheter showed obvious advantage in reducing abscess diameter (34.38?±?3.25 mm vs 22.67?±?2.37 mm, P=0.017). It can be concluded that the strong association with diabetes, milder clinical symptoms, and gas-forming nature in CT images makes early pathogenic diagnosis of KLA possible. Comparatively, ultrasonography-guided percutaneous liver aspiration with retained catheter may be the most rational intervention modality of KLA.