Two hundred three liver biopsies were performed on 114 patients suspected of having diffuse liver disease. More than one-half of the biopsies (107 of 203) were performed in liver allografts. Biopsies were performed under ultrasound (US) guidance with use of a spring-propelled 18-gauge cutting needle. Half of the biopsies were performed in patients with abnormal coagulation studies, decreased platelet counts, or both. The left lobe was chosen for biopsy over the right lobe in the majority of cases (112 vs 91). Sufficient tissue for diagnosis was obtained in 197 cases (97%). Four complications (2%) occurred that required treatment: one vasovagal reaction and three episodes of bleeding. All bleeding complications occurred in patients with coagulopathy. There was no difference in safety or efficacy between biopsies of native and transplanted livers; similarly, there was no difference in safety or efficacy between biopsies of the left and right lobe. Pain occurred less frequently with biopsies of the left lobe. US-guided biopsy with a spring-propelled 18-gauge needle is safe and efficacious in the diagnosis of diffuse liver disease.