BACKGROUND: Effective interventions to reduce the incidence of HIV, other sexually transmitted infections (STIs) and unwanted pregnancy among adolescents in sub-Saharan Africa are urgently needed. This paper describes the rationale and design of a randomised trial of the impact of an innovative sexual health intervention among adolescents in rural Mwanza Region, Tanzania. METHODS: The MEMA kwa Vijana intervention comprises a teacher-led, peer-assisted sexual health education programme for students in the last 3 years of primary school, training and supervision of health workers in the provision of youth-friendly health services, peer condom promotion and distribution, and wider community activities. Detailed process evaluation was conducted and the impact of the intervention was evaluated through a community-randomised trial in which a cohort of 9645 adolescents was followed up for 3 years. Both process and impact evaluation used multiple assessment methods. Impact measures included incidence and prevalence of HIV and other STIs, pregnancy rates, knowledge and reported attitudes and sexual behaviour, as well as qualitative assessments. RESULTS: Results of the baseline survey of the cohort have been presented previously. The outcome of the trial will be reported separately. CONCLUSIONS: Behaviour change interventions among adolescents have been widely advocated, but there have been few rigorously designed trials of their effectiveness, particularly in developing countries, and measurement of sexual behaviour is particularly problematic in this age group. The MEMA kwa Vijana trial was undertaken to address these problems and to collect rigorous evidence on the effectiveness of an innovative intervention, designed to be implemented on a very large scale.