A retrospective data analysis on liver transplantation for Wilson's disease (WD) was performed among Italian Liver Transplant Centers. Thirty-seven cases were identified. The main indication for liver transplantation was chronic advanced liver disease in 78% of patients. Mixed hepatic and neuropsychiatric symptoms were recorded in 32.3%. Eight patients presented with fulminant liver failure; 44.8% were on medical treatment. Patient and graft survival at 3 months, 12 months, 3 years, 5 years, and 10 years after transplantation were, respectively, 91.8%, 89.1%, 82.9%, 75.6%, and 58.8%, and 85.3%, 83.0%, 77.1%, 70.3%, and 47.2%. Neurological symptoms significantly improved after orthotopic liver transplantation (OLT), but the survival of patients with mixed hepatic and neuropsychiatric involvement was significantly lower than in patients with liver disease alone (P β«Ψβ¬ 0.04). WD characterized by hepatic involvement alone is a rare but good indication for liver transplantation when specific medical therapy fails. Patients with neuropsychiatric signs have a significantly shorter survival even though liver transplantation has a positive impact on neurological symptoms. In conclusion, a combination of hepatic and neuropsychiatric conditions deserves careful neurological evaluation, which should contraindicate OLT in case of severe neurological impairment. (Liver Transpl 2005;11: 1056-1063.) W ilson's disease (WD) is an inherited autosomal recessive copper accumulation and toxicity disorder that is estimated to affect about 1 in 30,000 people, with a carrier rate of 1 in 90. 1 The disease results from a copper-transport adenosine triphosphatase dysfunction in the liver that is responsible for excreting copper into the bile. 2,3 A number of mutations can impair protein function with subsequent copper accumulation occurring mainly in the liver, though toxic concentrations may also be found in brain, cornea, or kidney tissue. The disease is considered fully penetrant, so its diagnosis makes medical treatment mandatory, 4,5 based on copper chelating agents and zinc salts that take effect mainly by blocking intestinal copper absorption. 6 Compliance is essential because a rapid deterioration of the hepatic symptom has been reported after discontinuing anti-copper therapy. 7 Orthotopic liver transplantation (OLT) represents the ultimate treatment for this disease when medical therapy fails, 8 but the indication for, and timing of, this procedure have yet to be fully established: although the metabolic hepatic defect can certainly be treated, with survival rates reportedly ranging from 100% at 33 months 9 to 62% at 1 year, 10 the outcome of patients with neuropsychiatric symptoms after liver transplantation is still uncertain. Most studies have reported neurological improvement after OLT,11,12 simply describing every single case or by the use of very unspecific instruments like the performance status. Considering that the data available in literature on WD outcome after OLT are not yet conclusive and based on short-term follow-up, and that the issue of the neurological symptoms evolution has not been solved yet, in this paper we report a relatively large experience on liver transplantation for WD with a view to investigating which factors might affect post-OLT survival and the outcome of patients with associated neurological symptoms.