Ilio-psoas abscess is rare in neonates and is usually treated by surgical drainage. We report two cases of ilio-psoas abscess in 15- and 21-day-old infants successfully treated by US-guided percutaneous drainage as a supplement to antibiotic therapy. Clinical improvement was observed within 24-48 h of drainage and subsequent imaging demonstrated resolution of the abscess cavity. The analysis of these cases and of those previously reported indicates that imaging is essential for diagnosis. In neonates, US-guided percutaneous drainage may represent the first-choice treatment of this disease in association with antibiotic therapy.