A growing number of middle-income countries are scaling up youth-friendly sexual and reproductive health pilot projects to national level programmes. Yet, there are few case studies on successful national level scale-up of such programmes. Estonia is an excellent example of scale-up of a small grassroots adolescent sexual and reproductive health initiative to a national programme, which most likely contributed to improved adolescent sexual and reproductive health outcomes. This study; 1) documents the scale-up process of the Estonian youth clinic network 1991–2013, and 2) analyses factors that contributed to the successful scale-up. This research provides policy makers and programme managers with new insights to success factors of the scale-up, that can be used to support planning, implementation and scale-up of adolescent sexual and reproductive health programmes in other countries.