Transjugular liver biopsy was performed in a large series of patients for whom routine percutaneous biopsy was contraindicated; most of the patients had severe liver disease associated with coagulopathies or massive ascites. Of the 461 biopsies performed over a 7-year period, adequate specimens for histologic diagnosis were obtained in 425; in 14 (3.3%), the biopsy provided a false-negative result. Minor complications such as neck pain, hematoma at the puncture site, or pyrexia occurred in 79 patients (17.1%). Serious complications were encountered in six patients (1.3%) (two with cardiac arrhythmias; four with intraperitoneal hemorrhage following capsular perforation), with an overall mortality rate for the series of 0.22%. Modification of the technique--taking the biopsy with the catheter positioned centrally rather than wedged peripherally--has reduced the occurrence of capsular perforation without affecting the success rate. Transjugular liver biopsy is a valuable technique that provides diagnostic information in a high proportion of cases in which conventional percutaneous biopsy is contraindicated.