Background and Aims: Surgical resection is not always feasible in patients with hepatocellular carcinoma. Microwave coagulation therapy has been used as an alternative to resection, and its efficacy has been evaluated. Methods: Nineteen patients with unresectable hepatocellular carcinoma underwent microwave coagulation therapy through laparotomy (n=12), laparoscopy (n=5), or thoracotomy (n=2) because of advanced liver cirrhosis and/or intrahepatic metastases. One nodule was treated in 13 patients, and two to five nodules were treated in 6 patients; tumor size ranged from 5 to 90 mm. Patient outcomes were studied. Results: Microwave coagulation therapy created a reproducible regional necrosis. Fourteen patients underwent potentially curative treatment; the remaining 5 patients underwent palliative treatment (n =4) or incomplete tumor coagulation (n =1). Of the 31 nodules treated, 28 underwent complete tumor ablation. Only 2 patients undergoing laparoscopic microwave coagulation therapy developed local recurrence. The coagulated area subsequently shrank. Patients showed rapid recovery without hepatic dysfunction. Thirteen patients, including 2 long-term survivors, are alive either without tumor (n=10; 14 -64 months) or with tumor (n =3; 17 -22 months). Six patients died of hepatocellular carcinoma (n=4) or liver insufficiency (n=2). Conclusions: This preliminary study suggests the efficacy of microwave coagulation therapy, including safety and potential curability, in patients with hepatocellular carcinoma with advanced liver cirrhosis and multifocal or central tumors.