The risk of complications from percutaneous liver biopsy is low, but discomfort is common and complications require hospitalization in approximately 4% of patients. The optimal method of performing these biopsies is unknown. The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle. Between 1992 and 1994, 836 patients were entered into a randomized study (489 in Rochester, MN; 347 in Barcelona, Spain). Patients were randomized immediately prior to liver biopsy into four groups: Trucut needle, or automatic biopsy needle, and with or without ultrasonography. Fisher's Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications. The four biopsy groups were well-matched at entry with respect to age, sex, underlying liver disease, hemoglobin, prothrombin time, and platelet count. The use of ultrasound was associated with a decreased rate of hospitalization for pain, hypotension, or bleeding (2 vs. 9, P < .05). No difference in safety was found between the two types of needles. The number of passes needed to obtain specimens was similar for all four groups. The average length of the specimen was slightly greater with ultrasonographic-guided biopsies (1.7 mm vs. 1.6 mm, P < .05) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle (1.7 mm vs. 1.5 mm, P < .05), but this did not seem to be clinically important. The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy. The type of needle appears to offer little difference in safety or yield of diagnostic tissue. The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications. The value of this benefit must be weighed against the added cost of ultrasonographic guidance.