Background The advent of second generation agent-SonoVue and low mechanical index real-time contrast enhanced ultrasonography (CEUS) imaging have been shown to improve the diagnostic performance of ultrasonography in hepatocellular carcinoma (HCC). But no report has described the effect of high mechanical index (MI) post-CEUS. This study aimed to investigate the value of post-CEUS in displaying tissue structures of HCC. Methods Seventy-six HCCs in 65 patients were included in the study. Each patient underwent three scans, high-MI (MI: 0.15-1.6) pre-contrast ultrasound, low-MI (MI: 0.04-0.08) CEUS with contrast agent SonoVue, and high-MI post-contrast ultrasound, which was performed within 3 minutes after CEUS. The size, boundary, echogenicity, intal echotexture and posterior acoustic enhancement of the HCCs in the conventional scans before and after CEUS were evaluated. According to pathological evidence, diagnosis rates of pre-contrast, CEUS and post-contrast scans were determined and compared. The potential mechanism of post-contrast ultrasound imaging was also discussed. Results Compared with pre-contrast, post-contrast ultrasound showed improvement in image quality in most HCCs: twenty-six (34.2%) more lesions showed well defined margins and fourteen (18.4%) more nodules showed halo sign; twenty-three (30.3%) lesions demonstrated enlarged in sizes; changes in echogenicity were seen in 30 lesions (39.5%); eighteen (23.7%) more lesions showed heterogenecity and 20 (26.3%) more lesions showed mosaic or nodule-in-nodule sign; twelve (15.8%) more lesions showed posterior acoustic enhancement. Post-contrast ultrasound showed increased diagnostic accuracy of 93.4% (71/76), compare with 88.2% (67/76) of CEUS alone. Conclusions High-MI post-contrast ultrasound utilizes harmonic signals during the rupture of microbubbles, and significantly improves the display of echo-characteristics of HCCs in ultrasound images, which adds diagnostic values for CEUS. Post-contrast ultrasound could play an important role in tissue characterization, and may be included in CEUS protocols.