Background: Pyogenic hepatic abscess (PHA) is an uncommon infectious disease of the liver that should represents a life-threatening condition if not correctly diagnosed and managed. Nowadays there are not precise indications and clear evidences on the best therapeutic approach and on the superiority of a treatment. Methods: Patients with diagnosis of PHA admitted at the Policlinico “Paolo Giaccone” at Palermo University Hospital between January 2010 and December 2022 were identified in a prospective database. Among the demographic, epidemiological and clinical data collected we included the therapeutic choices – antibiotic treatment, image guided percutaneous drainage and surgical operation – and their effect in terms of healing time, treatment failure and time of hospitalization. Results: Patients with single abscesses treated with antibiotics have significant high healing time (p=0.0001) and in-hospital time (p=0.0001) and no differences in treatment failure than patients treated with invasive techniques. Patients that underwent surgical operation have significant higher healing time than percutaneous group (p=0.002) such as higher mean hospital stay (p=0.03 for abscesses <5 cm and p=0.02 for abscesses larger than 5 cm). The last, the percutaneous approach shows a failure rate significantly higher than the surgical procedure (p=0.009 for abscesses <5 cm and p=0.001 for abscesses larger than 5 cm). Conclusions: The study proposed showed the antibiotic therapy is the first line treatment and should first empirically and then directly modified on specimen culture results. Image guided percutaneous drainage should be considered when the antibiotic therapy alone is not sufficient or as bridge to surgery if surgical indications are proven.