South Africa's HIV prevalence among 15-24 year olds is one of the highest in the world. This systematic review looks at the evidence for youth HIV prevention in the country since 2000 and critically assesses interventions across four domains: study design and outcomes; intervention design; thematic focus and HIV causal pathways; and intervention delivery. Eight interventions were included in the review, all similar regarding content and objectives, but with variouis thematic foci, causal pathways, theoretical bases, delivery methods, intensity and duration. Interventions were based at schools (5) or group-based (3) and involved both in and out of school youth. Main outcomes were HIV incidence (2), sexual risk behavior (4) with alcohol use (2). Five interventions led to decreased sexual or alcohol risk behaviors andáone to decreased STI incidence. The majority of studies targeted a structural factor, including gender and sexual coercion (3), alcohol/substance use (2) or economic factors (2). Recommendations emerging from the study are a need to focus on HIV social risk factors and structural and institutional contexts, change social norms and find new ways of engaging at schools like through participatory learning.