Benign focal liver lesions (BFLLs) have become a common disease diagnosed in the clinical setting following the advancement of imaging techniques. The aim of the present study was to evaluate the safety and clinical outcomes of percutaneous microwave (MW) ablation, guided by ultrasound (US), for the treatment of BFLLs. Between May 2005 and January 2011, 44 BFLLs (mean maximum diameter, 33.9±13.1 mm) in 37 patients (23 women and 14 men) were treated by US-guided percutaneous MW ablation with cooled-shaft antennae. The pathological diagnosis of a BFLL was confirmed in 91.9% (34/37) of patients using a US-guided core needle biopsy prior to ablation. The BFLLs in the other 3 cases were diagnosed by typical presentations on contrast-enhanced imaging, as the patients refused to undergo biopsies. Five inclusion criteria, including indeterminate diagnoses of nodules on contrast-enhanced imaging prior to pathological verification, were recommended. The median follow-up period was 27.0 months (range, 6-73 months). The mean MW ablation energy and time were 55.0±41.6 kJ (range, 13.5-207 kJ) and 1,039.9±706.2 sec (range, 270-3,450 sec) per lesion, respectively. In total, 40 nodules (90.9%) were completely ablated, and no evidence of recurrence was demonstrated on contrast-enhanced imaging follow-up. The other 4 nodules (9.1%) were partially ablated due to the proximity of adjacent vital organs. Minor complications without sequelae included local pain and transient hemoglobinuria and no major complications occurred in peri-ablation. Overall, US-guided percutaneous MW ablation is a safe, effective and minimally invasive therapy for BFLLs in selected patients who are non-surgical candidates.