Three-dimensional contrast-enhanced ultrasound (3D-CEUS) is a combination of three-dimensional ultrasound (3DUS) and contrast-enhanced ultrasound (CEUS). To evaluate the feasibility of 3D-CEUS in liver imaging, investigate possible influencing factors to its image quality, and evaluate the influence of 3D-CEUS to clinical outcome, low acoustic power (mechanical index, 0.08-0.13) 3D-CEUS was carried out in 102 focal liver lesions in 92 patients by using the LOGIQ 9 ultrasound scanner and a volume transducer (frequency range, 2-5 MHz; focusing ability, 2-25 cm in depth; azimuth aperture 5.9 cm). The lesions were classified into two groups: group 1 (n=51) for characterization and group 2 (n=51) for local treatment response evaluation. The factors that influenced the image quality of 3D-CEUS were analyzed. The image quality and usefulness of 3D-CEUS between the two groups were compared by using the chi(2)-test. The results showed that the lesion diameter, location, and scanning route had no significant influence on the image quality in both groups, whereas interfering factors damaged the image quality in group 1. In group 1, during arterial phase, high image quality was more frequently found in hyperenhanced and hypo- or non-enhanced lesions compared with isoenhanced lesions. In group 2, interfering factor and local treatment response had no obvious influence on the image quality. The visualization rate of high image quality was 94.1% (48/51) in group 2 vs. 72.6% (37/51) in group 1 (P=0.012). The investigators found that 3D-CEUS improved confidence but made no change in diagnosis in 19 (37.3%) of 51 lesions in group 1, whereas 41 (80.4%) of 51 lesions in group 2 (P=0.000). 3D-CEUS tends to obtain better image quality and lead to higher diagnostic confidence in the lesions for local treatment response evaluation, and perhaps is more useful in this aspect in future clinical settings.