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Introduction Sub-Saharan Africa (SSA), including Tanzania, is double-burdened with high rates of teenage pregnancy and new HIV infections among adolescent girls and young women (AGYW) aged 15–24 years. Moreover, pregnant AGYW living with HIV in SSA have poorer adherence and retention on HIV treatment and elevated risks of vertical HIV transmission to their infants, as compared with older women. This paper describes the methods for the ENGAGE project, aiming to investigate and optimise healthcare for prevention of vertical HIV transmission (commonly prevention of mother-to-child transmission (PMTCT)) for AGYW living with HIV in Tanzania.Methods and analysis ENGAGE uses a mixed-methods design to co-create and prototype an intervention package for pregnant/postpartum AGYW living with HIV through three phases in three Tanzanian regions. Phase 1 characterises the problem by investigating care engagement and outcomes in a cohort of N=10 147 AGYW receiving PMTCT services in routine healthcare. Phase 2 uses qualitative interviews to understand the social-structural drivers of care engagement from the perspective of AGYW, healthcare providers and community stakeholders and an evidence review of potential solutions. In phase 3, we will use findings from phase 1 and 2 to co-create (together with AGYW and healthcare providers) an intervention package to optimise PMTCT care for most at-risk AGYW. The co-creation will be done through an intervention development action cycle, where ideas are presented, feedback sought and refinements made iteratively via several workshops over about 6 months. The resulting co-created intervention package will be prototyped at selected facilities/communities and refined into a final version, ready for piloting for feasibility, acceptability and preliminary effect in a later phase. This protocol focuses on the co-creation phase 3 and its preceding phases 1 and 2.Ethics and dissemination ENGAGE has received ethical approval from the Tanzania National Health Research Ethics Committee (NIMR/HQ/R.8a/Vol.IX/4637), and the Swedish Ethical Review Authority (2024-05745-01) for analysis of data in Sweden. Findings will be disseminated to AGYW, healthcare providers, community stakeholders, health officials, researchers, policy makers and the wider local and global scientific community.