During 2010-2012, Oregon Health & Science University's Prevention Research Center, a Northwest Tribe, and the Northwest Portland Area Indian Health Board, collaborated to evaluate the Healthy & Empowered Youth Project, a school- and community-based positive youth development program for American Indian and Alaska Native high school students.The Native STAND (Students Together Against Negative Decisions) curriculum was enhanced with hands-on learning activities in media design to engage students in sexual and reproductive health topics covered by the curriculum. Guest speakers, field trips, and extracurricular activities were added to provide academic enrichment, engage students in cultural activities, and offer opportunities for career development. Students completed comprehensive pre- and post-surveys, and the authors conducted focus groups and key informant interviews with students and teachers. Data analysis was conducted during 2013-2014.Survey findings demonstrated improvements in student leadership and achievement, physical and mental health, and protective sexual health behaviors. The percentage of female teens reporting use of a condom the last time they had sex increased from 17% to 30%, and those who reported ever having been tested for sexually transmitted illnesses doubled from 12% to 24%. Focus group and interview findings indicated similar improvements in student self-esteem, life skills, health behavior, and engagement in community.The Healthy & Empowered Youth Project educated and empowered Native high school students on a variety of sensitive health topics. The media enhancements were central to the program's success, reinforcing and personalizing classroom lessons and generating health-related videos and posters that resonated with family and friends.