The present study aimed to evaluate the safety of high-intensity focused ultrasound (HIFU) treatment on peripancreatic arterial and venous blood vessels in patients with pancreatic cancer. This trial included 15 patients with pancreatic cancer (9 females and 6 males; age, 39-81 years; median age, 62 years). All patients underwent preoperative computed tomography (CT) or magnetic resonance imaging (MRI) and color Doppler flow imaging (CDFI) to assess the vascular hemodynamics of peripancreatic arterial and venous blood vessels pre-treatment. These patients were re-examined within 1 week post-HIFU treatment. Then, vascular adverse events were observed and followed up clinically. Prior to HIFU treatment, vessel involvement was recorded in 13 patients, including tumor lesions invading 19 veins and 14 arteries, which refers to the growth of pancreatic tumor lesions surrounding blood vessels, or tumor growth into blood vessels. In addition, 9 veins and 13 arteries were <1 cm from the lesions. The hemodynamic parameters of peripancreatic vessels were measured using CDFI, including mean blood flow velocity, peak systolic blood flow velocity, vascular resistance index, vascular pulsatility index, vascular diameter, vascular blood flow and other indicators, to assess vascular perfusion in CT/MRI. There were no significant differences in preoperative and postoperative hemodynamic data (P>0.05). Overall, HIFU demonstrated no negative effects on peripancreatic arterial and venous blood vessels in patients with pancreatic cancer, even with tumor lesions wrapped in blood vessels. In addition, no complications of vascular stenosis and vascular adverse events were observed in the present study.