The Ayoreo population constitutes one of Bolivia’s most vulnerable ethnic groups in terms of HIV/AIDS. Being a woman, indigenous, and a sex worker signifies belonging to a high-risk group. The aim of this study is to explore the Ayoreo sex workers’ and health agents’ perceptions of HIV/AIDS prevention programs in order to identify variables that could influence their success or failure. This study used an ethnographic methodology that included participant observation and semistructured interviews. In the data collection, participant observation and semistructured interviews with sex workers and key informants were conducted. Three themes emerged from the inductive data analysis: health prevention efforts, cultural inadequacy of prevention programs, and the eventuality of interventions. We conclude that nursing can develop culturally-adequate HIV/AIDS prevention interventions and programs as well as promote health within these populations.