Current HIV/STI prevention interventions for female-male couples in the US require an in-person modality and focus on specific subgroups. Digital health interventions may provide one solution to expand access to tailored, couples-based HIV/STI prevention-care interventions that appeal to male-female couples in the U.S. with varying vulnerabilities to HIV and other STIs. One couples-based digital health intervention has reduced male couples’ susceptibility to HIV and other STIs. The intervention used a hybrid format with individuals first completing a sequence of pre-determined modules (i.e., HIV/STI education, instructional videos, a searchable sexual health resources database, activities including an agreement builder) followed by completing the sequence jointly with their partner, and then ending with a finalized, comprehensive sexual agreement containing HIV/STI prevention items. To examine the acceptability of this theoretically-driven, couples-based digital health intervention for HIV/STI prevention, we conducted a multi-method pilot project with 28 female-male couples in New York State. Couples in this pilot reported high intervention acceptability (96%), and qualitative dyadic content and thematic analysis revealed explicit recommendations to enhance intervention relevancy for adapting the digital health intervention to meet their specific relationship and sexual health needs. Given these preliminary findings, we propose to conduct a novel, 3-year mixed method study guided by the Couples Interdependence Theory and the Assessment, Decision, Adaptation, Production, Topical experts, Integration, Training, and Testing model to adapt and pilot-test this digital health intervention to meet the needs of female-male couples. Dyadic data will be collected via: a) quantitative assessments at baseline, month 3 and 6; b) HIV/STI screening at baseline and month 6; c) 7 different paradata outputs (intervention use); d) individual exit interviews at month 6. Our specific aims are: (1) Adapt the intervention for couples using the proposed model with human-centered design. (2) Conduct a 6-month pilot RCT with 60 couples using a 2:2 block random allocation approach (intervention vs. 3-month, waitlist control), stratified by dyad HIV serostatus. Feasibility will measure enrollment and retention rates. Acceptability will leverage mixed methods from 3 data sources: qualitative - to contextualize intervention engagement; paradata - to describe intervention use over time; quantitative - to assess usability, sexual health behavior and general wellness. (3) Examine preliminary intervention impact: a) primary outcomes (mutual HIV/STI awareness; creation/adherence to a tailored relationship agreement, uptake/adherence of evidence- based biomedical strategies); b) secondary outcomes (Improvements in relationship dynamics including communication). Impact will be assessed via couples’ outcomes over time, between trial arms, and for all couples. This study has high publ...