Background: Wedge biopsy of the liver yields more accurate diagnosis of liver diseases than does needle biopsy, but is usually more invasive. We have designed a new method for laparoscopic wedge biopsy under local anesthesia with use of an ultrasonically activated scalpel. Methods: We performed wedge biopsy in seven patients with liver diseases. Under local anesthesia, two trocars punctured the abdomen and the edge of the liver was dissected with the scalpel. We evaluated the differences in operating time, grade of pain during/after the biopsy, changes of laboratory data and changes of body temperature, between seven wedge and 18 needle biopsies. Results: No differences were found in all factors between wedge and needle biopsies. Conclusions: This new method of laparoscopic wedge biopsy under local anesthesia was safe and more useful than needle biopsy. It was also no more invasive than needle biopsy.