Large-scale innovative, integrated, multifaceted adolescent sexual and reproductive health (ASRH) interventions are urgently needed in sub-Saharan Africa. Implementation through schools and health facilities may maximize intervention coverage and sustainability, however the impact of the use of these structures on intervention content and delivery is not well documented. This paper describes the rationale and design of a large-scale multifaceted ASRH intervention, which was developed and evaluated over three years in rural communities in Mwanza Region, North West Tanzania. The intervention comprised community mobilization, participatory reproductive health education in primary schools, youth-friendly reproductive health services and community-based condom provision for youth. We examine the effect of socioeconomic, cultural and infrastructural factors on intervention content and implementation. This paper demonstrates the means by which such interventions can be feasibly and sustainably implemented to a high standard through existing government health and school structures. However, the use of these structures involves compromise on some key aspects of intervention design and requires the development of complementary strategies to access out-of-school youth and the wider community.