Background: The Cochrane HIV/AIDS Trials Register is hosted at the Review Group’s satellite base, the South African Cochrane Centre. In 2004, the CRG provided a two-year contract for a full-time Trials Search Co-ordinator (TSC) to update the paper-based reference registry to an electronic, study-based register. Objectives: 1) To describe the current status of the Registry; and 2) to identify facilitators and challenges to hosting a Registry in a resource-constrained country. Methods: We conducted a secondary data analysis of paper and electronic documentation, journal and conference presentations arising from the Registry. Results: The study-based Registry is fully operational in Meerkat. Records are downloaded quarterly from major databases, de-duplicated, and the ‘study design’ field coded prior to importation into Meerkat. Quality control is performed by an epidemiologist coding a random sample of records. The Registry currently contains 2025 randomized controlled trials, 344 controlled clinical trials and 796 studies to be confirmed, with 872 hardcopy trial reports housed in a hanging-file library and linked to the database by a unique identification number. The Registry was innovative in adding Geographic Information Systems detail to map the location of trials resulting in three conference presentations and one journal paper. These achievements were facilitated by: 1) receipt of the Collaboration Exchange Fellowship in 2004 for TSC training in the UK; 2) conversion of the position from contract to permanent; and 3) use of the TSC’s specialized GIS skills. Challenges have included: 1) resignation of the TSC in 2007 with difficulty recruiting due to skills shortages; 2) isolation of the TSC from colleagues based overseas; and 3) costs of subscriptions in resource-constrained setting limiting access to journals and thus study design coding. Conclusions: Hosting a Registry in a resource-constrained setting presents challenges, but we have used innovation and dedication to achieve a world-class resource for our authors.