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BACKGROUND Pyogenic liver abscess (PLA) is a rare disease with an estimated incidence that varies widely across the globe, being as high as 115.4/100000 habitants in Taiwan and as low as 1.1-1.2/100000 habitants in Europe and Canada. Even though there are multiple microorganisms capable of producing an abscess in the liver, including Entamoeba histolytica , fungi, and viruses, most abscesses are derived from bacterial infections. The epidemiology of PLA in Mexico is currently unknown. AIM To describe the clinical, demographic and microbiologic characteristics of PLA in Mexico. METHODS This is a retrospective study carried out in two centers, and included patients seen between 2006 and 2018 with the diagnosis of pyogenic abscess. We collected demographic, clinical, and microbiological information, treatment, complications, and outcomes. A logistic regression analysis was used to determine the association between different variables and mortality rates. RESULTS A total of 345 patients were included in this study. 233 (67.5%) had confirmed PLA, 133 (30%) patients had no positive culture and negative serology and 9 (2.5%) had mixed abscesses. The mean age was 50 years (ranging from 16-97 years) and 63% were female. 65% of the patients had positive cultures for Extended Spectrum Beta-Lactamases (ESBL)- Escherichia coli and Klebsiella pneumoniae . Cefotaxime was administered in 60% of cases. The most common sources of infection were ascending cholangitis and cholecystitis in 34 (10%) and 31 (9%), respectively. The median length of hospital stay was 14 d. 165 patients underwent percutaneous catheter drainage. The inpatient mortality rate was 63%. Immunocompromised state [OR 3.9, 95%CI: 1.42-10.46], ESBL- Escherichia coli [OR 6.7, 95%CI: 2.7-16.2] and Klebsiella pneumoniae [OR 4-8, 95%CI: 1.6-14.4] predicted inpatient mortality by multivariate analysis. CONCLUSION The prevalence of PLA is increasing in Mexico and has a very high mortality rate. ESBL- Escherichia coli and Klebsiella pneumoniae are the most common microorganisms causing PLA and are independent predictors of inpatient mortality.