This study was designed to evaluate the safety, efficiency, effectiveness, and overall long-term outcome in patients treated with microwave thermal ablation of hepatic tumors. Microwave ablation technology represents the next generation in ablative techniques for the treatment of hepatic malignancies. Currently there have been no large reports of its use in the United States with appropriate long-term follow-up. An institutional review board-approved prospective phase II study of microwave ablation of hepatic malignancies from January 2004 to January 2009 was performed. All complications were recorded up to 90 days from operation and reported using an established five-point grading scale. One hundred patients underwent 270 ablations for hepatic malignancies. The most tumor types were as follows: metastatic colorectal cancer (50%), hepatocellular carcinoma (17%), metastatic carcinoid (11%), and other metastatic disease (22%). A majority of patents (53%) underwent combination hepatic resection and microwave ablation; 38% underwent ablation alone, 9% underwent ablation and additional organ resection, with 68% open procedures. Median tumor size was 3.0 (range, 0.6-6.0) cm, median number of tumors was 2 (range, 1-18), and median total ablation time was 13 (range, 5-45) min. Overall 90-day mortality was 0% and morbidity was 29%. One patient developed a hepatic abscess and no patients experienced bleeding complications. After a median follow-up of 36 months, 5 patients (5%) had incomplete ablation, 2 (2%) had local recurrence at the ablated site, and 37 (37%) developed intrahepatic recurrence at nonablated sites. Microwave ablation of hepatic tumors is a safe and effective method for treating unresectable hepatic tumors, with a low rate of local recurrence.