The NIDDK Liver Transplantation Database was established to prospectively investigate questions related to the experience of patients evaluated for and undergoing liver transplantation. This article presents the study design, methods, and quality of data collection, along with some of the overall results. Methods: An initial 4-year planning phase was used to develop data collection instruments and quality control procedures regarding assessment for transplantation, liver donors, and the recipients' pre-, peri- and postoperative course. During the 1990-1995 implementation phase, three clinical centers refined the data collection instruments and enrolled and followed consecutive liver transplant candidates who consented to be included in the protocol. Results: The Database contains more than 49,000 data forms from 1563 candidates, 1002 donors, and 916 transplant recipients followed up to 5 years after transplantation. Overall, 95% of protocol forms were completed. The Database includes uniformly defined histology results of liver biopsies performed per protocol and for complications throughout follow-up. In addition, the Database maintains an inventory of available sera for the Serum Bank. All test results of studies performed on the sera are added to the Database. Of 1563 evaluated patients, 59% were deemed eligible for liver transplantation. Of the others who were too well or had contraindications, 15% became eligible later. Characteristics of patients in this study were generally comparable to those of patients nationally. Conclusions: The NIDDK Liver Transplantation Database has yielded comprehensive and high quality data and is a rich resource for extensive analysis about many important clinical aspects of liver transplantation.