Medical therapy is standard for intrahepatic amebic abscess and generally is effective. However, we have encountered a group of patients in whom percutaneous aspiration and drainage was indicated due to uncertainty of diagnosis or clinical deterioration of the patient. Twenty such patients underwent percutaneous drainage with ultrasound or CT guidance, and each patient was cured (appropriate antibiotics were administered concomitantly). The specific indications for intervention were to differentiate pyogenic from amebic abscess, pain and imminent rupture, poor response to medical therapy, false-negative results of serologic tests, noncompliance with medical treatment, left lobe abscess, and pregnancy. Diagnosis of amebiasis from examination of the fluid was seldom possible, while findings from core biopsy of the wall of the abscess led to diagnosis in three cases. Recurrence necessitating redrainage occurred in three patients; in each, catheters were removed the same day drainage was performed. There were three minor complications. Differences from percutaneous management of pyogenic abscesses included more rapid removal of catheters (four days), more frequent use of US guidance, and more common use of the prone angled approach to avoid pleural contamination. Catheter drainage may be curative and may expedite care for problematic amebic liver abscesses in selected cases.