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Introduction: Adolescents are experiencing high rates of depressive symptoms, with negative consequences to their long‐term health. Group‐based, mindful self‐compassion programs show promise in mitigating the development of more significant depression in at‐risk adolescents. However, the lack of well‐designed, active control conditions has limited the ability to examine the efficacy of such interventions. Methods: Fifty‐nine adolescents (Mage = 15.81, 70% female) with subsyndromal depressive symptoms from the Southeastern US were randomized to group‐based Mindful Self‐Compassion for Teens (N = 30) or a newly developed active control Healthy Lifestyles group (N = 29) during 2018 and 2019. Participants attended 8 weekly "main" sessions followed by 6 monthly continuation sessions. The feasibility and acceptability of participation in both groups were measured using attrition, attendance, credibility, and satisfaction data. Depression scores were collected weekly, and self‐compassion scores were collected five times across 36 weeks. Results: Both groups were equally feasible and acceptable during the 8‐week program period; however, monthly continuation sessions were poorly attended in both groups. The risk of developing clinically significant depression was 2.6 times higher in the control group compared with the self‐compassion group (p =.037) across 36 weeks. Depression significantly decreased in the self‐compassion group, while it significantly increased in the control group. Both groups increased significantly in reports of self‐compassion. These findings are on par with results noting the efficacy of cognitive‐based interventions for high‐risk adolescents; follow‐up studies with larger sample sizes should be conducted to confirm these findings. Conclusions: Initial examination suggests Mindful Self‐Compassion for Teens programming is feasible, acceptable, and efficacious in preventing the development of clinically significant depression in adolescents with subsyndromal depression. Future studies may benefit from refinements to the self‐compassion measurement and/or the attention control condition; moreover, larger sample sizes are needed to confirm results. [ABSTRACT FROM AUTHOR]