The purpose of this meta-analysis was to identify and evaluate the effectiveness of school-based social interaction interventions for adolescents with autism spectrum disorder (ASD). All 27 studies meeting predetermined inclusion criteria utilized single-case designs. Peer-mediated interventions, peer networks, behavioral skills training, and the teaching interaction procedure were the most frequently utilized strategies and produced large effects for lower, moderate, and higher functioning adolescents with ASD. Teachers rarely implemented interventions, though large effects were reported when they served as intervention agents. Future research concerning the acceptability and feasibility of using social interaction interventions in the classroom is needed in order to facilitate evidence-based practice. Additionally, research that targets more complex and nuanced social behaviors and assesses collateral effects such as academic performance and friendship quality appears warranted.