This study examined the effect of an interactive instrument playing program on the social interaction of adults with autism spectrum disorder (ASD). A single subject design with multiple baselines across participants was applied, and three adults with severe ASD in their late 20s living at a group home participated in this study. Participants received a total of 25 group sessions. During the intervention, participants engaged in structured instrument playing in which initiation and response to socially interactive behaviors were musically cued, and target behaviors were reinforced in the musical environment. At pre- and posttest, the frequency of initiation of and responding to social interaction behaviors were recorded and analyzed. The results of this study showed that the frequency of both initiation of, and response to, social interaction increased for all participants during the intervention phase, compared to the baseline phase. This result demonstrates that interactive instrument playing increased social behaviors of adults with ASD. It also shows that musically delivered social information can facilitate adults with ASD understanding the intention of social partners in social contexts and motivate this population to engage in social interaction.