ObjectiveTo investigate the clinical features and prognosis of culture-negative liver abscess (CNLA) versus culture-positive liver abscess (CPLA), and to provide a reference for early diagnosis and effective treatment. MethodsA retrospective analysis was performed for the clinical data of 371 patients with liver abscess who were admitted to The Second Affiliated Hospital of Air Force Medical University from 2005 to 2018, among whom 145 (39.1%) had positive results of pathogen test (CPLA group) and 226 (60.9%) had negative results (CNLA group). The two groups were compared in terms of clinical features, laboratory examination, imaging data, and prognosis. The t-test was used for comparison of normally distributed or approximately normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the CNLA group, the CPLA group had a significantly older age (t=-3.464, P=0.001) and a significantly higher proportion of patients with diabetes (χ2=17.362, P＜0.001) or cardiovascular disease (χ2=10.827, P=0.001), and compared with the CPLA group, the CNLA group had a significantly higher proportion of patients with AIDS (χ2=4.354, P=0.037). Compared with the CNLA group, the CPLA group had significantly greater increases in leukocyte count, percentage of neutrophils, alkaline phosphatase, gamma-glutamyl transpeptidase, and total bilirubin (U=20393, 19711, 18586, 19349, and 18496, all P＜0.05), a significantly greater reduction in albumin (t=3.348, P=0.001), and a significantly higher proportion of patients with a baseline APACHE Ⅱ score of ≥16 (χ2=9.550, P=0.002). Compared with the CNLA group, the CPLA group had a significantly higher proportion of tumors with a diameter of ＞5 cm (χ2=53.61, P＜0.001). In the CNLA group, 19.9% of the patients were treated with anti-infective therapy alone, while for both groups, anti-infective therapy combined with ultrasound- or CT-guided percutaneous drainage was the main treatment method. There were no significant differences in the length of hospital stay, recurrence rate, and mortality rate between the two groups (all P＞0.05). ConclusionCompared with CPLA patients, CNLA patients tend to have a younger age and are less likely to develop severe inflammatory response and liver insufficiency, with a smaller diameter of abscess which is less likely to be treated by percutaneous drainage, while there is no significant difference in prognosis between CPLA patients and CNLA patients.