PURPOSE: Neglected tropical diseases (NTDs) affect people living in the poorest regions of the world and their debilitating effects perpetuate the poverty cycle. Understanding the distribution of NTDs is crucial for effective intervention delivery. In 2012, the Global Trachoma Mapping Project (GTMP) was initiated to map >1800 suspected trachoma endemic districts by March 2015. This research was carried out to better understand the implementation experience and identify lessons which might inform the GTMP and similar initiatives. METHODS: Using grounded theory methodology, semi-structured interviews were conducted with key informants from six countries with 63% of the global mapping backlog (Ethiopia, Malawi, Mozambique, Nigeria, Solomon Islands, and Yemen). Interviews were transcribed, coded, and findings separated into categories. RESULTS: Three themes were identified during the research; planning and operations, technical implementation, and governance. The project was felt to be most successful in countries where the Ministry of Health was actively engaged in setting standards, ensuring capacity building for government staff, and guiding the training, data collection, analysis, and interpretation of data. Standardized tools, training platforms, and the use of electronic data capture increased confidence in the reliability of the survey data, informed quality improvement efforts within survey implementation, and the immediate release of results empowered end-user decision-makers. Regional collaboration between endemic countries bolstered program manager competence and confidence, while reinforcing partnerships essential to the success of the GTMP. CONCLUSIONS: We depict how innovative characteristics of the GTMP, and lessons learned from its implementation, can strengthen similar initiatives to map disease prevalence and risk factors.