A nationwide prospective study was conducted in France in 89 university and primary referral hospitals' liver units to evaluate practices of liver biopsy and the occurrence of complications. A total of 2,084 biopsies were analyzed, recording the indication, hemostasis parameters, experience of operator, route of biopsy, use of ultrasonography (US), type of hospitalization, side effects, and complications. Pain, anxiety, and discomfort were evaluated by patients by visual analogue scale (VAS). Biopsies were performed by experienced physicians (>150 procedures performed) in 72%, and hepato-gastroenterologists in 89% of the cases. Hepatitis C was the indication in 54%. Sedation or premedication (atropine) was given in 46%. US-guidance was used in 56% of the cases. A day-care procedure was used in 27%. No deaths occurred, but severe complications were observed in 0.57% and increased with the number of passes and decreased with experience of operator, use of atropine, and US-guidance. Pain was independently related to general anesthesia, experience of the operator, female sex, and hepatitis C. Anxiety was increased in women. Discomfort was increased by venous access and decreased with an experienced operator. Acceptance of additional biopsies was related to a day-care procedure and independently related to general anesthesia and multiples passes. This study showed that (1) liver biopsy procedures vary greatly in France, (2) hepatitis C is the main indication for liver biopsy at present, (3) US-guidance should be developed to reduce severe complications, and (4) day-care procedures increase acceptance of a future biopsy and should also be used more often.