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Background: Adult pyogenic liver abscess (PLA) is a major hepato-biliary infection. We aim to identify risk factors associated with therapy failure., Methods: Retrospective study of 741 PLA patients (2001-2011) and comparison with earlier data (1994-1997). Risk factors associated with therapy failure were identified with multivariate analysis., Results: Incidence of PLA is 86/100 000 admissions, with average size 5.75 cm. 68% of PLA were secondary to Klebsiella pneumoniae and there is increasing extended-spectrum beta-lactamase (ESBL) resistance. Compared with 1990s, there is an increasing annual incidence (from 18 to 67). Elderly age (≥55-years-old), presence of multiple abscesses, malignancy as etiology and patients who underwent endoscopic intervention are independent predictors for failure of antibiotics-only therapy while average intravenous antibiotics duration and average abscess size are not. ECOG performance status ≥2, pre-existing hypertension and hyperbilirubinaemia are independent predictors for failure of percutaneous therapy while the presence of multiple abscesses and average abscess size are not., Conclusion: There is an increasing PLA incidence with increasing ESBL resistance. Percutaneous drainage should be considered early for elderly patients (≥55-years-old), with multiple abscesses, malignancy as etiology or who required endoscopic intervention. We should have a low threshold for surgical intervention for patients with ECOG performance status ≥2, co-morbidity of hypertension or hyperbilirubinaemia., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)