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Background: Adolescents and young adults (AYA) aged younger than 25 years have the highest rates of sexually transmitted infections (STIs) in the United States. Current STI prevention strategies for AYA rely primarily on individual approaches, leaving sexual partners with significant unmet sexual and reproductive health care and health education needs. Dyadic interventions may hold promise for harnessing the power of communal coping within relationship dynamics to enhance sexual decision making, communication, and behavior changes that reduce the future risk of STIs. Objective: This paper describes the protocol and research methods of a dyad-based behavioral intervention that augments individual evidence-based interventions with joint health education counseling for heterosexual AYA dyads within a primary care setting. The trial aims to improve partner communication and collaborative sexual decision making and promote the adoption of sexual behaviors such as consistent condom use. The primary objective of this study is to assess the feasibility, acceptability, and effectiveness of a dyadic intervention targeted at preventing STIs in heterosexual couples in an urban setting. Methods: A total of 100 AYA (50 dyads) aged 16 to 25 years, engaged in heterosexual intercourse, who reside in the city and are willing to recruit their main sexual partner for the study will be recruited and randomized into 2 groups, an intervention arm and a control arm. Participants will be recruited from an AYA medicine clinic and by using social media (Facebook and Instagram). The index participant and partner will complete a single individual session separately (Sister to Sister or Focus on the Future) with a gender-matched health educator. Dyads will then be randomized to receive an additional joint debriefing session together to discuss relationship dynamics, condom negotiation, etc. Participants will separately complete a telephone interview 6 weeks postintervention to determine the feasibility, acceptability, and impact of the intervention on mutual sexual negotiation, consistency of condom use, and communal coping skills, etc. Results: So far, 25.4% (44/173) of eligible participants have been enrolled and randomized. Participants are mostly female (20/22, 91%), with at least a high school diploma (19/22, 86%), and 9 average lifetime sexual partners. Acceptability is high, with 98% (43/44) of participants expressing satisfaction with their study experience; 100% of dyads recruited were still together at 6-week follow-up. Conclusions: Findings from this study will add to the current literature on the approaches to STI prevention, and its success will inform its application in risk reduction counseling for youth who are most at risk. [ABSTRACT FROM AUTHOR]