BACKGROUND In western countries, there has been a gradual shift from Escherichia coli to Klebsiella pneumoniae as an emerging pathogen isolated from pyogenic liver abscesses (PLA). OBJECTIVE To compare outcomes between patients with Escherichia coli liver abscesses and non-Escherichia coli liver abscesses in terms of mortality. METHODS One hundred nine-three consecutive hospital admissions of Pyogenic liver abscesses were analyzed, mean age 66.9 years old (± 13.6), 112 men (58%). The sample was divided into two groups: E. coli liver abscesses and non-E. coli liver abscesses. The etiologic, clinical, and microbiologic characteristics; therapeutic options; and outcomes, in terms of morbidity and mortality, between E. coli and non-E. coli liver abscesses were compared. In-hospital mortality, as outcome variable, was analyzed in a multivariate analysis. RESULTS Fifty-seven episodes of PLA (29.5%) corresponded to E. coli infections, and 136 (70.5%) to non-E. coli infections. Patients with E. coli PLA were more likely to have jaundice, polymicrobial isolation (57.1% vs 21.6%, p < 0.001), biliary origin (71.9% vs 39%, p < 0.001), and septic shock (38.6% vs 12.5%, p < 0.001). Antibiotic therapy alone, without percutaneous drainage, was less common in the E. coli PLA group (5.3% vs 18.4%, p = 0.018). These patients also showed a higher mortality (28.1% vs 11%, p = 0.003). In multivariate analysis, E. coli isolation PLA adjusted remained as an independent factor of mortality (OR 2.6, 95%CI 1.04-6.56, p = 0.041). CONCLUSIONS E. coli liver abscess may preclude a worse outcome than other microbiological agents, including the development of septic shock and mortality. Aggressive management must be considered.