The authors conducted a process evaluation of the 10-fold scale-up of an evaluated youth-friendly services intervention in Mwanza Region, Tanzania, in order to identify key facilitating and inhibitory factors from both user and provider perspectives. The intervention was scaled up in two training rounds lasting 6 and 10 months. This process was evaluated through the triangulation of multiple methods: (1) a simulated patient study; (2) focus group discussions and semi-structured interviews with health workers and trainers; (3) training observations; and (4) pre- and post-training questionnaires. These methods were used to compare pre- and post-intervention groups and assess differences between the two training rounds. Between 2004 and 2007, local government officials trained 429 health workers. The training was well implemented and over time, trainers' confidence and ability to lead sessions improved. The district-led training significantly improved knowledge relating to HIV/AIDS and puberty, attitudes toward condoms, confidentiality, and young people's right to treatment. Intervention health units scored higher in the family planning and condom request simulated patient scenarios, but lower in the sexually transmitted infection scenario than the control health units. The scale-up faced challenges in the selection and retention of trained health workers and was limited by various contextual factors and structural constraints. Youth-friendly services interventions can remain well delivered, even after expansion through existing systems. The scaling-up process did affect some aspects of intervention quality, and this research supports others in emphasizing the need to train more staff (both clinical and non-clinical) per facility in order to ensure youth-friendly services delivery.