Developing an effective vaccine remains a critical long-term approach to HIV prevention. Every efficacy trial should be responsive to the concerns of participating communities because the successful development of an HIV preventive vaccine will require long-term involvement of people who have been marginalized and who distrust the government and biomedical research. Using qualitative interviews and purposive sampling, we elicited recommendations regarding how vaccine efficacy trials should be conducted from 90 members of communities that have been disproportionately affected by HIV/AIDS: injection drug users, gay men, and African Americans. The most common recommendation was for complete disclosure of all aspects of the trial. Other themes included participant and community education, who to include in trials, preventing harm, trust, community involvement, researcher attributes, and respect for participants. Developing positive, respectful and collaborative experiences with community members will facilitate vaccine research because negative experiences and unfavorable community reactions can greatly impede success in future trials.