Aim The increasing volume of tests (∼5% growth per year) processed by the Histocompatibility laboratory has gradually become an overwhelming challenge. The current Laboratory Information System (LIS) Oracle database has generated a substantial amount of manual and redundant data entry while only offering limited interface capabilities without meeting the changing regulatory reporting requirements. This manual input has contributed to inefficiency and transcription errors while lack of interfaces has significantly increased the paperwork. In 2011, the decision was made to implement a replacement LIS to address these issues. Methods The HistoTrac software available from SystemLink was chosen to meet our needs. Workflow considerations were subsequently made with strategies developed for maintaining an existing information system while implementing its replacement. A detailed timeline with major milestones and their estimated durations was established to monitor progress with support from the vendor. The laboratory IT team performed all major data migration, software upgrades and interface development as well as testing, validation and training. After going live in May 2012, the cost savings and improvement in Turn Around Time (TAT) have been closely monitored. Results External databases and most laboratory equipment were integrated with HistoTrac to support a seamless data transfer and reduce manual transcription. Middleware (i.e. Excel macros) were developed to format data exported from HistoTrac specifically to fit instrument requirements. Significant cost savings in all areas of the laboratory ($93,000) was realized. The TAT was improved on average by a day for both High and Mediums resolution HLA typing tests. Conclusions A well designed cost-effective information system is essential for a laboratory to stay competitive. The new LIS dramatically reduced the clerical labor required to handle information, increased the accuracy of patient reports, and significantly sped up reporting of results to providers. The connection of automated instruments to the LIS is perhaps the most important aspect of the system. Without these bi-directional interfaces, the system will not be fully functional.