In 2007, 48% of U.S. students of grades 9 to 12 had experienced sexual debut, 7% before the age of 13 years. Preventing early intercourse, sexually transmitted diseases, adolescent pregnancy, and the loss of educational opportunity are important concerns for nurses and educators. A secondary data analysis of the Youth Risk Behavior Survey (YRBS) 2003 provided data identifying the relationships among age at sexual debut, gender, location of residence, and perceived school safety (PSS) as framed by the theory of problem behavior. Mean age at sexual debut was 14.4 years. Males were younger at sexual debut than females. Students reporting positive PSS were older at sexual debut. Age at sexual debut was significantly associated with PSS, gender, and location of residence. School nurses are positioned to identify evidence-based programs, facilitate the development of collaborative interventions to improve PSS, and change trajectories of sexual activity leading to poor health outcomes in adolescents and health risk behaviors in adults. (Contains 2 tables.)