Both enduring neurotic vulnerabilities and economic hardship have been shown to negatively influence marital behaviors, which have physical and mental health consequences. However, because most previous research is fragmented and has focused on the early years of marriage or relatively short periods of time, their long-term effects are unclear. Using data from the Iowa Midlife Transitions Project, with a sample of 370 married couples providing data from 1991 to 2001, we assessed enduring personal and couple vulnerabilities, trajectories of family economic hardship, and couples' marital hostility using a comprehensive dyadic model to ascertain their influence on subsequent mental health. Couple marital hostility trajectories and neurotic vulnerabilities (both additively and interactively) were associated with changes in both spouses' depressive symptoms. Results also indicated that couples' marital hostility trajectories link trajectories of family economic hardship to subsequent changes in husbands' and wives' depressive symptoms. Last, associations between economic hardship trajectories, marital hostility trajectories, and depressive symptoms were moderated by couples' neurotic vulnerability as captured by a product term of husbands' and wives' neurotic vulnerability. In general, these associations were amplified for couples with a high level of couple vulnerability and weakened (or altogether absent) for those with a low level of vulnerability. (PsycINFO Database Record (c) 2018 APA, all rights reserved).