The present study tested the relationships among conscientiousness-related traits, social-environmental factors that affect health, and substance-use behaviors across a 30-year period from age 21 to age 52 in the Mills Longitudinal study of women (N=99). Results showed that the trait of social responsibility (a facet of conscientiousness) assessed at age 21 predicted family, work, and substance use outcomes at midlife (age 43 and age 52). In turn, marital quality, duration of marriage, divorce, participating in paid work, status level of work, and marijuana consumption were associated with changes in social responsibility. The implications for personality, health, and personality development are discussed.