Objective: The therapeutic response of radio-frequency ablation (RFA) for hepatocellular carcinoma (HCC) was evaluated by contrast-enhanced ultrasonography (US) using a new contrast mode, agent detection imaging (ADI), and its usefulness was compared with that of dynamic computed tomography (CT). Materials and methods: Forty patients with 64 nodules diagnosed as HCC histologically and/or by various imaging modalities were evaluated with ADI (1 and 7 days after treatment) and Dynamic CT (7 days after treatment). Results: ADI and dynamic CT revealed residual lesions in 15 and 12 nodules, and no residual lesions in 45 and 52 nodules, respectively. ADI yielded indeterminate findings in four nodules; although the vascular phase showed minute residual tumor vessels, the tumor appeared to be completely contained within the ablated area in the delayed phase. In these indeterminate cases, US-guided biopsies of the areas of residual vascularity revealed no viable cancer cells; only degenerated tissues. Conclusion: In assessing the therapeutic response of RFA for HCC, ADI has a similar competence to dynamic CT. Even if the vascular phase of contrast-enhanced US shows minute residual vessels, as long as the tumor is safely contained within the ablated area in the delayed phase, the cancer cells are likely to be degenerated.