Autism spectrum disorder (ASD) is a condition of early childhood onset characterized by profound deficits in social interaction, impaired communication and repetitive behavior. The prevalence of ASD is now estimated to be one in 100 children. As the number of identified cases of ASD has grown, so have the challenges of serving these children and their families. Unfortunately, the empirical foundation for many interventions for this population is not firmly established. Thus, there is a pressing need to conduct trials that will expand the evidence base and guide clinical treatment. Investigators from the Research Units in Pediatric Psychopharmacology (RUPP; Indiana University, IN, USA; Ohio State University, OH, USA; University of Pittsburgh, PA, USA; and Yale University, CT, USA) followed a treatment development model outlined by an National Institute of Mental Health ad hoc committee to develop and test a parent training treatment manual for children with ASD accompanied by disruptive behavior problems. This article describes the process of manual development and cross-site therapist training, establishment and maintenance of treatment integrity, assessment of treatment acceptance by families as well as primary outcomes of three trials. Results suggest the structured parent training program can be delivered with a high degree of fidelity within and across therapists, is acceptable to parents and can produce significant reductions in disruptive behaviors in children with ASD.