This report highlights the 2024 achievements of the O3 PLUS programme, implemented in six Eastern and Southern African (ESA) countries: Kenya, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe. Launched in 2021, the O3 PLUS programme builds on the success of UNESCO’s Our Rights, Our Lives, Our Future (O3) programme, Africa’s largest comprehensive sexuality education (CSE) initiative, to empower students in HTEIs across the ESA region to make informed decisions about their health and well-being. Unlike secondary school students, HTEI students often navigate new levels of independence, unfamiliar relationships, and unique pressures. The programme seeks to ensure that young people (aged 18-24) in HTEIs realize positive health, education, and gender equality outcomes through sustained reductions in new HIV infections and unintended pregnancies, as well as protection from GBV. The O3 PLUS programme has made substantial strides across its objectives, focusing on enhancing institutional sustainability, student health and well-being, campus safety, and evidence-based programming. The programme’s emphasis on institutional ownership and student participation and agency has been crucial for its success. By empowering students and institutional representatives as agents of change, the programme has created a ripple effect, amplified the impact of interventions, and promoted a culture of student health and well-being.