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To develop a method of dynamic three-dimensional (3-D) simulation of thermal distribution in ultrasound-guided microwave coagulation therapy of liver cancer and to verify its accuracy. The specific absorption rate (SAR) values were established by measuring the temperature in equivalent phantom tests. Those values were different under different power output condition. Dynamic 3-D temperature distributions were reconstructed with a finite-element model. Testing and rectification were performed through animal experiments and clinical trials, respectively. The temperature curves in the experiments corresponded well with simulated ones in vitro-91.3% and 88.9% using single and double electrodes, respectively. The measured coagulated boundary and simulated temperature boundary had a good correspondence in 85.7% of the specimens. In both in vivo experiments and clinical trials, blood perfusion influenced the rise in temperature significantly. Temperature curves between the simulations and actual measured results showed good correspondence-67.8% (19/28) in the patients with hepatocellular carcinoma. Distance between electrodes and combined thermal distributions were both optimized with computer-aided simulation during simultaneous two-electrode coagulation. The results demonstrated that computer-aided simulation of microwave thermal distribution is an accurate and reliable method which provides a theoretical and technical basis for controlling coagulated tissue volume and placement of the electrodes during microwave coagulation therapy of liver cancer.