OBJECTIVES: To evaluate uptake of a complex intervention for HIV prevention among general populations of adolescent girls and young women (AGYW) in three diverse settings. DESIGN: Cohorts of ∼1500 AGYW were randomly selected from demographic platforms in Kenya (Nairobi and Siaya) and South Africa (uMkhanyakude, KwaZulu-Natal). METHODS: AGYW aged 13/15-22 years were enrolled in 2017 (Nairobi and uMkha-nyakude) or 2018 (Siaya), with annual follow-up to 2019. We describe awareness of DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored and Safe), self-reported invitation to participate, and uptake of DREAMS interventions by: categories and levels of the PEPFAR core package;number of 'primary' interventions (seven in Kenya;five in South Africa). Analyses were stratified by year invited and age at cohort enrolment. RESULTS: Proportions aware and invited to DREAMS increased across all settings, to ≥ 83% aware and ≥ 53% invited by 2018 (highest among AGYW aged 13-17 years, e.g. 63 vs. 40% among 18-22 s, uMkhanyakude). HIV testing, school-based interventions and social protection were the most accessed categories, while differences in uptake by DREAMS invitation were greatest for novel DREAMS interventions, for example, social asset building (76% among those invited in 2017 and 2018 vs. 9% among those never-invited in Nairobi). Although few DREAMS invitees accessed all intended primary interventions by 2019 (2% of 15-17 s and 5% of 18-22 s in Gem), many accessed at least three interventions, including combinations across individual, family and community levels. CONCLUSION: Over time, DREAMS reached high proportions of AGYW in all settings, particularly younger AGYW. Participation in combinations of interventions improved but uptake of the complete primary packages remained low.