--- - |2+ Background Parental mental disorders have been shown to predict offspring's mental health problems. We examined whether pathways from parental mental disorders to offspring's psychiatric work disability in early adulthood are mediated through offspring's mental disorders and social disadvantage in adolescence. Methods Study population consisted of the 1987 Finnish Birth Cohort. Data on parents’ psychiatric care or work disability due to mental diagnosis between 1987 and 2000 and the cohort participants’ health and social factors between 2001 and 2005 were derived from administrative national registers. From 2006 through 2015, 52,182 cohort participants were followed for admittance of psychiatric work disability due to depressive or anxiety disorders. First, we applied a pathway analysis to examine the occurrence of each path. We then used mediation analysis to assess the proportion of association between parental mental disorders and work disability mediated by offspring's health and social disadvantage. Results The pathway model indicated that the association from parental mental disorders to offspring's work disability due to depressive or anxiety disorder is through mental disorders and social disadvantage in adolescence. Odds Ratio for the total effect of parental mental disorders on offspring's psychiatric work disability was 1.85 (95% confidence interval [CI] 1.46–2.34) in the model including offspring's mental disorders that mediated this association by 35%. Corresponding results were 1.86 (95% CI 1.47–2.35) and 28% for social disadvantage in adolescence. Conclusions These findings suggest that intergenerational determination of work disability due to mental disorders could be addressed by actions supporting mental health and social circumstances in adolescence. - Depression and Anxiety, EarlyView.