Background: Young people whose parents suffer from depression have a greatly elevated risk of developing a psychiatric disorder but poor outcomes are not inevitable. Identifying what contributes to mental health resilience in young people at high familial risk is an internationally recognised priority. Our objectives were to identify protective factors that predict sustained good mental health in adolescents with a depressed parent and to test whether these contribute beyond what is explained by parent illness severity. Methods: Parents with recurrent major depressive disorder, co-parents, and offspring (aged 9-17 years at baseline) were assessed three times over four years in a community setting (n=262). Offspring outcomes were operationalised as i) absence of mental health disorder, sub-threshold symptoms or suicidality on all three study occasions (sustained good mental health); ii) better than expected mental health (mood and behavioural symptoms at follow-up lower than predicted given severity of parental depression). Family, social, cognitive and health behaviour predictor variables were assessed using interview and questionnaire measures. Findings: Adolescent mental health problems were common, but 20% (n=53) exhibited no problems. Co-parent support, good quality social relationships and self-efficacy predicted all outcomes. Frequent exercise contributed to sustained good mental health and better than expected mood-related mental health. Index parents’ expression of positive emotions about their child predicted sustained good mental health and better than expected behavioural mental health. Multiple protective factors were required for offspring to be free of mental health problems (0-1 protective factors: 0-5% sustained good mental health, 2-3 protective factors: 10-13%, 4-5 protective factors: 38-48%). Interpretation: Adolescent mental health problems are common, but not inevitable, even when parental depression is severe and recurrent. Findings suggest that prevention programs will need to enhance multiple protective factors across different domains of functioning. Funding: Sir Jules Thorn Charitable Trust, Economic and Social Research Council.