This study was carried out to explore the role of knowledge on reproductive health in influencing the transmission of Sexual Transmitted Infections (STIs) to adolescent. Their knowledge is very vital towards combating a negative health outcome such as their vulnerability to STIs and unwanted pregnancy. The study was conducted in Mkalama District involving Gunda and Iambi secondary schools owing to cost reduction and time limit. A cross sectional comparative study was carried out from 16th to 27th February 2015. Structured questionnaires were administered to 329 respondents whom were 303 students and 26 teachers from selected schools through stratified and purposive sampling techniques. Analysis of data was through Statistical Package for the Social Sciences (SPSS) after consistency data checking and cleaning. The findings showed that more than half (67.7%) of the adolescent had an average knowledge on Reproductive Health Care (RHC). In spite of the knowledge they had, yet more than half of the respondent (53.1%) did not know signs and symptoms of STIs. Majority of both students (98.7%) and teachers (81%) were aware of the incorporation of RHC in the curriculum and also agreed that knowledge on RHC was provided to adolescent who are in school as per curriculum. The sources of RHC knowledge to adolescent in this study were identified to be teachers, parents, doctors/nurses, friends, sister, mass media and brother. Therefore there is a need for the government to increase adolescent knowledge on RHC in order to overcome negative health outcome. Special emphasize should be on the signs and symptoms of STIs which was low in this study. For instance have special sustainable educative program through the media, work shop, peer education and printed materials for easier access to upgrade their knowledge on RHC.