Pregnancy is a time of relative urgency and opportunity for the treatment of substance use disorders in women, yet little is known about modifiable factors that contribute to successful abstinence. We examined self-worth, depression, anxiety, and novelty seeking in the context of substance use cessation during pregnancy in a sample of women with a high prevalence of substance abuse. Subjects were 448 birth mothers who participated in a prospective adoption study. Discontinuation rates were: tobacco 22.2%, alcohol 64.7%, marijuana 77.2%, and other drugs, 73.7%–100%. Depression, anxiety, and novelty seeking were lower among women who discontinued substance use, compared to those who did not. Self-worth was higher in women who discontinued substance use. Among 110 polysubstance users, the number of substances discontinued during pregnancy was correlated with depression, anxiety, and self-worth in the hypothesized direction. Possible clinical implications are discussed.