Postpartum depression affects a substantial proportion of new mothers in the United States. Although most employed women return to paid work after birth, the association between duration of maternity leave and postpartum depression is unclear. We therefore aimed to explore this relationship among mothers in the United States.Data included 177 mothers from a national survey who had returned to work full time after having a baby. Multivariable logistic regression was used to explore the independent association between duration of maternity leave and experiencing of postpartum depressive symptoms in the 2 weeks preceding the postpartum survey completion.Overall, duration of maternity leave was not significantly associated with experiencing postpartum depression symptoms (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.80-1.01). This effect, however, varied by duration of maternity leave. Among women who took maternity leaves of 12 weeks or less, every additional week of leave was associated with a lesser odds of experiencing postpartum depressive symptoms (OR, 0.58; 95% CI, 0.40-0.84). Among women who took maternity leaves longer than 12 weeks, leave duration was not associated with postpartum depression symptoms (OR, 0.97; 95% CI, 0.73-1.29).Maternity leaves equaling 12 weeks or less may contribute additional risk for postpartum depressive symptoms, possibly because mothers are juggling employment alongside of important physical and emotional changes during this period. This association underscores the importance of ensuring that mothers have at least 12 weeks of leave from full-time employment after the birth of a baby.