Background: This study examines the effectiveness of the culturally adapted Dutch version of The Program for the Education and Enrichment of Relational Skills (PEERS®), utilizing a randomized control trial (RCT) with an active treatment control condition. Methods: 106 adolescents with ASD, aged 12–18 years, were randomly assigned to one of two group interventions: the experimental condition (PEERS®; n = 54) or the active treatment control condition (Regulation, Organization and Autonomy Didactics; ROAD; n = 52). Effects of interventions on social skills were primarily assessed using an observational measure (CASS – Contextual Assessment Social Skills). Secondary indices of social skills were self, parent and teacher reported questionnaire data (i.e., Social Responsiveness Scale; SRS, and Social Skills Improvement System; SSIS). Treatment satisfaction was also obtained from adolescents and their parents. Results: Results on the observational measure of social skills revealed improvements in positive affect, overall quality of rapport, as well as starting and ending a conversation, irrespective of condition. Compared to ROAD, PEERS® participants showed increased overall self-reported social skills (SSIS). Parent reports showed decreased overall social skill impairment (SRS) as well as improved social communication (SSIS subscale), with significantly more progress in the PEERS® group. Furthermore, parents of adolescents in the PEERS® group were significantly more satisfied with the intervention (M = 8.20, SD = 1.46) than parents of adolescents in the ROAD group (M = 7.52, SD = 1.45). The self-reported treatment satisfaction of adolescents did not differ between conditions. Teacher data showed decreased social skill impairment as measured with the SRS, irrespective of condition. Conclusions: This study reveals promising indications that the Dutch version of PEERS® enhances social skills in adolescents with ASD. Yet, further research is needed into how effectiveness can be optimized. Trial registration: Dutch trail ...