As in other countries worldwide, adults with severe mental illness in Brazil have elevated rates of HIV infection relative to the general population. However, no HIV prevention interventions have been tested for efficacy with psychiatric patients in Brazil. We conducted participatory research with local providers, community leaders, patient advocates, and patients using an intervention adaptation process designed to balance fidelity to efficacious interventions developed elsewhere with fit to a new context and culture. Our process for adapting these interventions comprised four steps: (1) optimizing fidelity; (2) optimizing fit; (3) balancing fidelity and fit; and (4) pilot testing and refining the intervention. This paper describes how these steps were carried out to produce a Brazilian HIV prevention intervention for people with severe mental illness. Our process may serve as a model for adapting existing efficacious interventions to new groups and cultures, whether at a local, national, or international level.