This case study presents methods and analyses used to understand the implementation of a national HIV prevention strategy for El Salvador, which was funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). The national combination prevention strategy involved multiple sectors and organizations in a coordinated effort to prevent HIV among men who have sex with men, female sex workers, and transgender women by reducing their sexual risk behaviors, increasing the number of those who know their HIV status, linking people living with HIV to care, and treating people living with HIV with antiretroviral medications with sufficient adherence to achieve viral suppression and prevent the spread of HIV to others. Similar national strategies have proven challenging due to systems barriers across sectors and organizations. Our research on the national plan in El Salvador aimed to identify some of the systemic barriers and successes in increasing coordination across organizations and sectors to eliminate the spread of HIV. We used in-depth interviews with actors in each of the organizations involved in the national plan to understand their roles in the strategy, patterns of communication and decision making, and successes and challenges in implementing the strategy. Analyses used a systems framework to identify forces that impeded or reinforced HIV prevention efforts. In this case study, we describe missed opportunities in data collection and challenges we confronted in using a systems framework in analysis.