The "Program for the Education and Enrichment of Relational Skills" (PEERS®) is an intervention targeting social skills for autistic adolescents and those with other social challenges. The efficacy of the PEERS® on adolescents has been extensively explored but the program has not been validated in Italy. In the present study, we adapted PEERS® to Italian culture and evaluated its efficacy in an Italian sample. A Randomized Controlled Trial was conducted, analyzing the results of 37 autistic adolescents who were randomly assigned to two groups: experimental group (TG) and waitlist group (WL). The primary outcomes (social abilities) and secondary outcomes (co-occurring conditions, executive functions) were assessed at four time points. No differences were found at pre-treatment between groups on baseline measures and primary outcomes. At post-treatment, significant group differences emerged in primary outcomes (social knowledge and social performance) and secondary outcomes (emotion regulation). The groups' results pooled together (TG + WL) confirmed the findings at post-treatment and showed further changes in primary outcomes (global social competence and social cognition) and secondary outcomes (externalizing problems, emotive and behavioral total problems, functional problems related to depressive symptoms). The improvements were maintained at a 3-month follow-up, except for global social competence and social cognition. Additionally, new results emerged regarding internalizing problems and global executive functioning. The efficacy of the Italian version of PEERS® was ascertained on primary and secondary outcomes. Innovative findings on emotion regulation, behavioral problems, and depression symptoms also emerged.