OBJECTIVE: To examine whether contrast-enhanced ultrasound (CEUS) parameters in patients with advanced pancreatic cancer could be used to assess response to treatment with pulsed-wave high intensity focused ultrasound (PW-HIFU). METHODS: We prospectively recorded the pretreatment and posttreatment CEUS related parameters, CA19-9, pain scores of 30 patients with advanced pancreatic cancer treated with PW-HIFU treatment. Correlation of clinical parameters, tumor characteristics, and PW-HIFU treatment energy with CEUS parameters were analyzed. RESULTS: Pain score decreased after treatment (from 4.80 +/- 2.14 to 3.28 +/- 1.93, p = 0.001). CA19-9 dropped in RT decreased group, 4 weeks after one session PW-HIFU, compared with prolonged group (p = 0.013). According to the display of blood vessels in the mass by CEUS, tumors were classified by vessel grade (VG), VG1: no vessel can be seen; VG 2: vessels diameter <5 mm; VG 3: vessels diameter >5 mm VGs were different between increased and decreased relative rise intensity (rRI) groups (p = 0.008). VG1 group shown a decreased rRI after treatment, while VG3 group showed the opposite trend (p = 0.006). CONCLUSIONS: CEUS can evaluating response to PW-HIFU in advanced pancreatic cancer. Quantitative analysis may help to assess the short-term efficacy of patients and help for individualized treatment.