This case study concerned clinical safety and behavioral-pharmacological intervention with an 18-year-old man who had autism spectrum disorder and high-frequency aggression toward care providers at a specialized school. A multicomponent behavior support plan included antecedent, differential reinforcement, environmental modification, and physical management procedures subsequently combined with psychotropic medication (aripiprazole). Clinical safety components emphasized comprehensive care provider training, continuous supervision, function-based treatment, and prevention-focused strategies. The behavioral-pharmacological intervention eliminated implementation of aggression-contingent physical restraint and was associated with increased transition compliance during the school day. Throughout the 7.5 months duration of the study, there were no injuries to the participant or other students and a single injury was sustained by one care provider. Intervention effects were long-standing, and care providers rated their training, implementation fidelity, and therapeutic outcome favorably.