This study compared adjustment and quality of relationship in siblings of adolescents and young adults with Autism Spectrum Disorder (ASD; n = 27) and siblings with typical development (n = 27). Siblings completed the Network of Relationships Inventory-Behavioral Systems Version and Symptom Checklist-90-R. Only for siblings of adolescents and young adults with ASD, we conducted in-person semi-structured interviews for evaluating the sibling relationship in terms of similarity and differences, siblings' demands, and feelings. Results demonstrated that the two groups showed different emotional relationship and adjustment. A qualitative survey lead to several interesting suggestions to plan support's projects for adolescents siblings and young adults. The findings of this study emphasize the importance of carefully considering the domains included in future research on individual's psychological well-being and quality of sibling relationship for planning intervention programs siblings of adolescents and young adults with Autism Spectrum Disorder.