OBJECTIVE: We investigate how risk of sexually acquiring or transmitting HIV in adolescent girls and young women (AGYW) changed following the real-world implementation of DREAMS (Determined, Resilient, Empowered, AIDS free, Mentored and Safe) HIV prevention programme. DESIGN: A representative population-based prospective cohort study of AGYW living in rural KwaZulu-Natal. METHODS: Between 2017 and 2019, we interviewed a random sample of AGYW aged 13-22 years annually. We measured exposure to DREAMS as self-reported receipt of an invitation to participate and/or participation in DREAMS activities that were provided by DREAMS implementing organizations. HIV and herpes simplex virus type 2 (HSV-2) statuses were ascertained through blood tests on Dried Blood Spot (DBS). We used multivariable regression analysis to assess the association between exposure to DREAMS and risk of acquiring HIV: measured as incident HSV-2 (a proxy of sexual risk) and incident HIV;and the risk of sexually transmitting HIV: measured as being HIV positive with a detectable HIV viral load (≥50 copie/ml) on the last available DBS. We adjusted for sociodemographic, sexual relationship, and migration. RESULTS: Two thousand one hundred and eighty-four (86.4%) of those eligible agreed to participate and 2016 (92.3%) provided data for at least one follow-up time-point. One thousand and thirty (54%) were exposed to DREAMS;HIV and HSV-2 incidence were 2.2/100 person-years [95% confidence interval (CI) 1.66-2.86] and 17.3/100 person-years (95% CI 15.5-19.4), respectively. There was no evidence that HSV-2 and HIV incidence were lower in those exposed to DREAMS: adjusted rate ratio (aRR) 0.96 (95% CI 0.76-1.23 and 0.83 (95% CI 0.46-1.52), respectively. HIV viral load was detectable for 169 (8.9%) respondents;there was no evidence this was lower in those exposed to DREAMS with an adjusted risk difference, compared with those not exposed to DREAMS, of 0.99% (95% CI-1.52 to 3.82]. Participants who lived in peri-urban/ urban setting were more likely to have incident HIV and transmissible HIV. Both HSV-2 incidence and the transmissible HIV were associated with older age and ever having sex. Findings did not differ substantively by respondent age group. CONCLUSION: DREAMS exposure was not associated with measurable reductions in risk of sexually acquiring or transmitting HIV amongst a representative cohort of AGYW in rural South Africa.