An ultrasound-guided double pass biopsy technique using a large bore cutting needle via an anterior subcostal route (USAB) is described. The diagnostic adequacy of this biopsy procedure was evaluated in comparison with the traditional Menghini technique in 200 cases of suspected chronic liver disease randomly assigned to the two different procedures. Retrieval rate was better in the USAB group. The sample length was less than 15 mm in four cases in the USAB group and in 19 cases in the Menghini group. In three cases in the USAB group the second pass modified the diagnosis of the first specimen from chronic active hepatitis to active cirrhosis. In order to evaluate the safety and discomfort of the two procedures 340 patients assigned to the different techniques had liver ultrasound scans 6 and 24 h following percutaneous biopsy. USAB was associated with a reduced frequency of complications (one out of 170 patients vs. seven out of 170 patients who had the intercostal Menghini procedure). In our study, USAB seems to offer better sampling and size of individual samples, together with reduced frequency of major and minor complications.