ABSTRACT: Suicide attempts are strong predictors of suicide, a leading cause of adolescent mortality. Suicide attempts are highly familial, although the mechanisms of familial transmission are not understood. Better delineation of these mechanisms could help frame potential targets for prevention.To examine the mechanisms and pathways by which suicidal behavior is transmitted from parent to child.In this prospective study conducted from July 15, 1997, through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age,?17.7 years) of 334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a suicide attempt, were followed up for a mean of 5.6 years.The primary outcome was a suicide attempt. Variables were examined at baseline, intermediate time points, and the time point proximal to the attempt. Participants were assessed by structured psychiatric assessments and self-report and by interview measures of domains hypothesized to be related to familial transmission (eg, mood disorder and impulsive aggression).Among the 701 offspring, 44 (6.3%) had made a suicide attempt before participating in the study, and 29 (4.1%) made an attempt during study follow-up. Multivariate logistic regression revealed that proband suicide attempt was a predictor of offspring suicide attempt (odds ratio [OR],?4.79; 95% CI, 1.75-13.07), even controlling for other salient offspring variables: baseline history of mood disorder (OR,?4.20; 95% CI, 1.37-12.86), baseline history of suicide attempt (OR,?5.69; 95% CI, 1.94-16.74), and mood disorder at the time point before the attempt (OR,?11.32; 95% CI, 2.29-56.00). Path analyses were consistent with these findings, revealing a direct effect of proband attempt on offspring suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive aggression as a precursor of mood disorder.Parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting for the familial transmission of mood disorder. Interventions that target mood disorder and impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal behavior.