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Objective: This study investigated the relationship between social roles (marriage, employment, parenthood) and depressive symptoms and whether role accumulation (number of roles) versus specific role configurations (e.g., married parent) matter more for mental health by gender. Method: Utilizing data from the National Longitudinal Survey of Youth (N=7,614), we estimated depressive symptoms with regression models during the first decade of midlife – from 40 to 50 years old. Results: The relationship between role accumulation and depressive symptoms is curvilinear, with the decrease in depressive symptoms flattening at higher numbers of roles. Role configurations that include employment (e.g., married and employed) produced the lowest levels of depressive symptoms for both women and men. Discussion: Social roles were generally good for mental health at midlife, but role gains and losses were more detrimental for women. Role configurations that did not include employment (e.g., parent only) increase depressive symptoms more for men than women.