The purpose of this study was to determine if tissue harmonic imaging (THI) sonography produces higher quality images of the liver than conventional sonography. A prospective study was performed on 91 anatomic areas (60 liver tumors, 31 vascular structures) in 44 patients to compare the image quality of THI sonography with that of conventional sonography. THI sonography transmits at 2.0 MHz and receives at 4.0 MHz, while conventional sonography is used at 2.5 MHz or 4.0 MHz. All anatomic areas were studied by THI and by conventional ultrasonography at 2.5 MHz and at 4.0 MHz. Observers who were blinded to the sonographic technique ranked the quality of the obtained images. THI was the best technique for the evaluation of liver tumors, at an intermediate depth (p<0.0001) (4-8 cm from the body surface), but not for assessing superficial (4 cm or less) or deep (over 8 cm) tumors. THI was ranked as the best technique for examination of vascular structures regardless of depth. There was statistical difference at an intermediate depth (p<0.0001), but no significance was found for deep vascular structures (p=0.061). The number of superficial vascular structures was too small for statistical analysis. THI sonography is more useful than conventional ultrasonography for the study of vascular structures and intermediate-depth liver tumors, but is not always adequate for superficial or deep anatomic areas.