There is a strong need for inexpensive, easily administered HIV and STD prevention interventions that are highly replicable and appealing to diverse clinic audiences. This article describes the four-step iterative and collaborative process used by the Safe City Study Group to design and develop a brief video-based intervention: Safe in the City. Step 1 involves identification of an appropriate intervention medium, a theoretical framework, and key messages; Step 2, collaboration with a film company to integrate the framework and key messages into an entertaining product; Step 3, facilitation of a multistep participatory process involving input from members of the priority audience (clinic patients), clinic staff, and community reviewers; and Step 4, pilot-testing to determine structural barriers to patients' viewing the video in clinic waiting rooms. Safe in the City has been demonstrated to reduce incident STDs among clinic patients in three cities in the United States.