Background: The Interactive Systems Framework (ISF), a guide for translational research, encourages the balancing of traditional research and community-based participatory research (CBPR) approaches.

Objectives: This paper focuses on the challenges, solutions, and lessons learned in applying the ISF to our translational research project.

Methods: A community–campus partnership translated evidence-based screening guidelines on sexually transmitted infections (STIs) and depression into culturally relevant educational materials. Community health workers (CHWs) disseminated the information through a cross-over design to Hispanic women in Pima County, Arizona. Challenges, solutions, and lessons learned were identified throughout this process.

Lessons Learned: We identified challenges in the areas of research design, and in the ISF systems of prevention synthesis and translation, prevention support, and prevention delivery. We successfully negotiate solutions between the scientific and local community that resulted in acceptable compromises for both groups.

Conclusions: The model presented by the ISF is difficult to achieve, but we offer concrete solutions to community members and scientists to move toward that ideal.