BackgroundIn a parallel randomized controlled trial the effectiveness of the family- and group-based cognitive-behavioural “Gug-Auf” intervention in preventing depression in children of depressed parents was evaluated. We hypothesized that the intervention would be associated with reduced incidence of depression at 15 months as well as with reduced symptom severity at 6, 9, and 15 months. We also explored the role of a number of mediators and moderators.MethodsFamilies were included if a parent (n = 100, mean age = 46.06, 61% female) had experienced depression and children (n = 135, aged 8–17 years, 53% female) had no mental illness. Families (91.5% German) were randomly allocated (50:50 block-wise; stratified by child age and parental depression) to the 12-session “GuG-Auf” intervention or no intervention. Outcomes were assessed (on an intention-to-treat basis) at 0-(T1), 6-(T2), 9-(T3) and 15-months (T4) after baseline. Primary outcome (onset of depression; T4) was assessed with standardized (blinded) clinical interviews. Secondary (unblinded) outcome was risk of depression (at T2-T4) indicated by self- and parent-reported symptoms of internalizing, externalizing and depressive disorder. Potential mediators were emotion regulation, attributional style, knowledge of depression and parenting style. Potential moderators were parental depression severity and negative life events.ResultsNone of the children who received the intervention developed depression, whereas two of those in the control group did. The intervention significantly reduced depression risk (indicated by severity of self-reported internalizing symptoms) at T3 (p= .027,d= -0.45) and T4 (p= .035,d= -0.44). Both groups showed reduced depressive symptoms (p= .029,d= -0.44). Cognitive problem-solving and negative parenting emerged as mediators. There was no evidence that the intervention was associated with parent-reported internalizing symptoms or externalizing symptoms. No adverse events were observed.ConclusionsChildren of parents with depression showed an increase in self-reported (but not parent-reported) internalizing symptoms over time. This increase was not present in children who received the GuG-Auf intervention. The intervention was not associated with changes in externalizing symptoms. Conclusions regarding prevention of the onset of depression were not possible. Despite some limitations in the generalizability, these findings contribute to reducing the burden of youth depression.RegistrationThe trial was registered on 16/04/2014 at ClinicalTrials.gov (NCT02115880) and study protocol published in BMC Psychiatry (https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-014-0263-2).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-023-04926-2.