High school is an important time in the educational career of students. It is also a time when adolescents face many behavioral, academic, and social-emotional challenges. Current statistics about the behavioral, academic, and social-emotional challenges faced by adolescents, and the impact on society through incarceration and dropout, have prompted high schools to direct their attention toward keeping students engaged and reducing high-risk behavioral challenges. The purpose of the study was to examine the effects of School-Wide Positive Behavioral Interventions and Supports (SW-PBIS) on the levels of individual student problem behaviors during a 3-year effectiveness trial without random assignment to condition. Participants were 36,653 students in 12 high schools. Eight schools implemented SW-PBIS, and four schools served as comparison schools. Results of a multilevel latent growth model showed statistically significant decreases in student office discipline referrals in SW-PBIS schools, with increases in comparison schools, when controlling for enrollment and percent of students receiving free or reduced price meals. In addition, as fidelity of implementation increased, office discipline referrals significantly decreased. Results are discussed in terms of effectiveness of a SW-PBIS approach in high schools and considerations to enhance fidelity of implementation.