ICAP at Columbia University (ICAP) has supported strengthening of health information systems (HIS) in the Kingdom of Lesotho from 2014 to 2024 through two different projects. Both projects were funded by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC). Although they had a specific focus on HIV/AIDS data, their support expanded to strengthening health data systems in general. The most recent project—Support of Strategic Information Activities in the Kingdom of Lesotho (ICAP SI_II) under PEPFAR (Cooperative Agreement [CoAg] # NU2GGH002219-03-00)—began on September 30, 2019, and ended on September 30, 2024. It focused on: i) strengthening the monitoring and evaluation (M&E) capacity of MOH and district levels to produce high-quality data; ii) conducting data quality assessments (DQAs) for PEPFAR Monitoring, Evaluation, and Reporting (MER) indicators in hospitals and health centers; iii) enhancing evidence-based programming by utilizing data from multiple sources; iv) strengthen health information systems specifically, DHIS2 and eRegister systems, including improving interoperability of DHIS2 with other data systems (e.g., Data for Accountability, Transparency and Impact Monitoring [DATIM], Laboratory Information System [LIS], eRegister). The project also aimed to transition implementation and leadership of SI activities to local partners, specifically the Ministry of Health (MOH), Lesotho, the National University of Lesotho (NUL), and district health managers. After its five-year duration, this end-of-project evaluation aimed to determine the progress made in leading and strengthening SI activities in Lesotho within the project scope and share results with all relevant stakeholders to inform future considerations in the country.