ABSTRACT: In South Africa, HIV prevalence among youth aged 15-24 is among the world's highest. Given the urgent need to identify effective HIV prevention approaches, this review assesses the evidence base for youth HIV prevention in South Africa.Systematic, analytical review of HIV prevention interventions targeting youth in South Africa since 2000. Critical assessment of interventions in 4 domains: 1) study design and outcomes, 2) intervention design (content, curriculum, theory, adaptation process), 3) thematic focus and HIV causal pathways, 4) intervention delivery (duration, intensity, who, how, where).Eight youth HIV prevention interventions were included; all were similar in HIV prevention content and objectives, but varied in thematic focus, hypothesised causal pathways, theoretical basis, delivery method, intensity and duration. Interventions were school- (5) or group-based (3), involving in- and out-of-school youth. Primary outcomes included HIV incidence (2), reported sexual risk behavior alone (4), or with alcohol use (2). Interventions led to reductions in STI incidence (1), and reported sexual or alcohol risk behaviours (5), although effect size varied. All but one targeted at least one structural factor associated with HIV infection: gender and sexual coercion (3), alcohol/substance use (2), or economic factors (2). Delivery methods and formats varied, and included teachers (5), peer educators (5), and older mentors (1). School-based interventions experienced frequent implementation challenges.Key recommendations include: address HIV social risk factors, such as gender, poverty and alcohol; target the structural and institutional context; work to change social norms; and engage schools in new ways, including participatory learning.