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Following the discovery of hepatitis C virus, more liver biopsies (LB) than before are being performed to assess the severity of liver disease. In this study, following the recommendations for outpatient LB made by the Patient Care Committee of the American Gastroenterological Association, we assessed the feasibility and benefits of LB performed as an outpatient versus inpatient procedure over the last 7 years in our centre. The study included 1,581 patients consecutively examined in our institute; all LBs were performed by a single operator with a 16-gauge needle using the Menghini technique, and in all cases the puncture site was determined using prebiopsy ultrasound. Liver lesions were classified using grading and staging scores. Ultrasound-guided LB of focal lesions were excluded from this study. LB was performed on 1,318 outpatients and 263 hospitalized patients. The mean age of the hospitalized patients was higher than that of the outpatients (p < 0.0001). As major side effects, one death and one haemoperitoneum requiring blood transfusion were recorded in the hospitalized patients. As minor side effects, one haemorrhage occurred in the hospitalized patients, whereas a case of haemobilia and 2 cases of subcapsular haematoma were recorded in the outpatients. In both groups pain at the puncture site was the most frequent minor complication which easily resolved after non-steroid drug administration. Severe histological diagnoses, both in terms of grading and staging, were significantly associated with hospitalized patients. In conclusion, by carefully selecting patients and using prebiopsy ultrasound to assess the puncture site, outpatient LB can be safely performed in most cases; this procedure should be more widely used, because it has met with the favour of patients who are able to return home the same day and reduces public health care service costs.