This study explored the relationships among personal factors, family structure and family function, adolescents’ self-efficacy for safe sex, and sexual behaviors among sexually active adolescents. A subset sample from the first three waves of the National Longitudinal Study of Adolescent Health (Add Health) was selected for this exploratory secondary data analysis. Hierarchal and logistic regressions were conducted to explore the relationships among personal factors, family factors, and adolescents’ self-reported sexually transmitted infections (STI) over time. Findings suggest that adolescents’ racial/ethnic background, parents’ disapproving attitudes, and family connectedness are significant predictors for birth control and condom use among adolescents. Although adolescents’ personal factor and family structure play a role in their sexual behavior, positive family function significantly protects adolescents from STIs over time. School nurses can provide a vital point of care for at-risk adolescents by finding ways to encourage and incorporate parental and familial influences. (Contains 3 tables and 1 figure.)