Vaccination, one of public health’s greatest disease prevention tools, is broadening to focus on adolescents. Now that there are more vaccines targeted specifically for adolescents, it is time to give more focus to vaccine delivery in this population. This research will increase the knowledge base to support informed changes in adolescent vaccine delivery by identifying knowledge and attitudes of adolescents toward vaccination within the context of barriers and solutions. Perceived susceptibility to disease, benefits and barriers to vaccination and other constructs were collected through a survey to 1368 high school students. In this population, a scheduled adolescent healthcare visit is feasible, vaccine education can diminishes health misconceptions, and vaccination mandates are ways to reach some students.