The efficiency, accuracy, and safety of ultrasound-guided liver biopsy with plugging of the needle track were prospectively assessed in 72 patients at high risk for hemorrhage. Seventy-eight biopsy procedures were performed in 72 consecutive patients prospectively classified into four different groups on the basis of coagulation parameters. Sixty-two patients (86%) had severe or moderately severe coagulation disorders. Fifty-four biopsy procedures were performed in 50 patients with diffuse liver disease, and 24 were performed in 24 patients with focal liver lesions. The biopsy track was embolized with gelatin particles and thrombin. Biopsy specimens adequate for histologic diagnosis were obtained in 69 of the 72 patients (96%). In focal lesions, accuracy and sensitivity in the diagnosis of malignancy were 75% and 89%, respectively. Two serious bleeding complications (2.8%) were encountered in two of the patients with major coagulation disorders. Liver biopsy with plugging of the needle track is a practical technique and is a feasible alternative to the transjugular approach. Respective indications for both methods depend on the severity of coagulation disorders and the presence of focal lesions.