Key PointsQuestionAre early-life internalizing and externalizing problems associated with adulthood unemployment and work disability, and do familial factors (genetics and shared environment) play a role in the association?FindingsIn this cohort study of 2845 young Swedish twins prospectively followed over the transition to adulthood, both persistent internalizing and externalizing problems were associated with unemployment and work disability. After adjustment for familial factors, there was no association with unemployment, but associations with work disability remained similar.MeaningThese findings suggest that nonshared environmental factors may play a role in the longitudinal association of early-life mental health problems with adult work disability.