The authors evaluated the safety of ultrasound (US)-guided percutaneous ablation of liver tissue using a neodymium-yttrium-aluminum-garnet (Nd:YAG) laser fiber placed through a skinny needle. The US appearance of the lesion was correlated with the pathologic findings in 19 pigs killed at 1-7 weeks. A 20-gauge needle was percutaneously placed in the liver, and a fiber with a 0.5-cm cladding-stripped tip was inserted. The Nd:YAG laser was fired for 6 minutes at 1-4 W. The early sonographic appearance was recorded, and the US appearance before the pigs were killed was correlated with the gross and histopathologic findings. There were no cases of abdominal bleeding or infection. Mild transient changes in liver function were seen. An initial strong echogenic focus decreased slightly in echogenicity for 10 minutes and then stabilized. Over 1-7 weeks, the 1-cm-diameter lesion decreased in size and developed an echogenic rim that correlated with a peripheral zone of inflammatory repair around a small central cavity and zone of necrosis. US-guided laser ablation of liver tissue is safe in this pig model, and the US appearance corresponds to a process of repair and removal of necrotic liver tissue.