Purpose: To describe the development of the first disease prevention intervention with ultra-Orthodox Jewish (UOJ) women in Israel using mixed methods and community-based participatory research (CBPR). Design: This collaborative, 7-staged development process used an exploratory sequential mixed methods design integrated into a community-based participatory approach. Setting: The UOJ community in Israel, a high-risk, low socioeconomic, culturally insular minority that practices strict adherence to religious standards, maintains determined seclusion from mainstream culture and preserves traditional practices including extreme modesty and separation between the sexes. Participants: Women from a targeted UOJ community in Israel with distinct geographic, religious, and cultural parameters. These included 5 key informant interviewees, 5 focus groups with 6 to 8 participants in each, a cluster randomized sample of 239 questionnaire respondents (an 87% response rate), and 11 steering committee participants. Method: Qualitative data were analyzed through Interpretative Phenomenological Analysis by 2 researchers. Quantitative data were collected via questionnaire (designed based on qualitative findings) and analyzed utilizing descriptive statistics. Results: Barriers to health behavior engagement and intervention preferences were identified. The final intervention included walking programs, health newsletters, community leader trainings, teacher and student trainings, and health integration into schools. Conclusion: Utilizing mixed methods in CBPR improved cultural tailoring, potentially serving as a model for intervention design in other difficult to access, low socioeconomic, and culturally insular populations.