Abstract Purpose Despite about 5% of the US population identifying as Sexual and Gender Diverse (SGD), there is limited research on cancer prevention and control disparities in this population. In New Mexico (NM), population-level data from the Department of Health show differences in cervical and breast cancer screening uptake based on sexual orientation, but these data do not document disparities based on gender identity and for other types of cancer, prompting us to assess cancer prevention practices among NM SGD communities. SGD communities have consistently been considered “hard to reach” and much of the extant SGD studies have been conducted in large urban cities. We present findings on how to implement innovative, multi-pronged, and systematic recruitment strategies to engage SGD communities in NM, a state that is both largely rural and racially classified as “majority-minority” state. Methods Our recruitment efforts focused on four strategies: (1) Every Door Direct Mail program (by the United States Postal Services) was used to mail flyers across targeted (based on residential areas, income below $30,000, and between ages 30-71) mailing routes across NM. (2) These routes were also targeted for study-related ads via Google, Twitter, and Facebook. (3) Email outreach was conducted with SGD-friendly businesses, state cancer coalitions, and the University of New Mexico Comprehensive Cancer Center's Office of Community Outreach and Engagement. (4) Flyers were displayed at clinical and community settings across NM. All flyers, ads, and emails contained QR codes for a pre-survey that determined eligibility for participation in the main survey (i.e. 21-80 years old, NM resident, member of SGD community). Questions on the online survey, provided in both English and Spanish, inquired about the participant's demographics, body organs, physical health, vaccination history, healthcare access, and cancer screening practices. Results A total of 27,369 flyers were distributed and 436,177 impressions were made on social media, resulting in 5,080 surveys from eligible participants. Approximately 68% heard about the study from social media, 17% from email, 16% through friends or family, and 12% from flyers. All eligible participants were then emailed three times and, in a few cases, mailed a survey. This resulted in 3,115 completed surveys. Half of respondents were between 31-40 years, 38% were Black, Hispanic, or American Indian/Alaskan Native, and 48% had an annual household income below $50,000. Eighteen percent identified as lesbian, 30% gay, 28% bisexual, and 18% queer, while 48% were cisgender men, 32% cisgender women, and 13% transgender. Approximately 44% reported residing in rural areas and responses were received from 172 unique NM zip codes. Conclusion To reach state-wide SGD communities and engage them in population-based research, innovative and systematic efforts are needed. Social media and postal flyers may provide successful recruitment opportunities with potential to use these methods for future public health interventions for these populations. Citation Format: Prajakta Adsul, Karen Quezada, Katie Myers, Talya Jaffe, Bernard Tawfik, Emily Wu, Molly McClain, Shiraz Mishra, Miria Kano. Reaching the “hard to reach” sexual and gender diverse communities for population-based research in cancer prevention [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-080.