Up to 50% of mothers report postpartum depressive symptoms yet providers do a poor job predicting and preventing their occurrence. Our goal was to identify modifiable factors (situational triggers and buffers) associated with postpartum depressive symptoms. Observational prospective cohort telephone study of 563 mothers interviewed at 2 weeks and 6 months postpartum. Mothers reported on demographic factors, physical and emotional symptoms, daily function, infant behaviors, social support, and skills in managing infant and household. Mothers were categorized into four groups based on the presence of depressive symptoms at 2 weeks and at 6 months postpartum: never, always, late onset, and remission groups. Fifty-two percent did not have depressive symptoms at 2 weeks or at 6 months (never group), 14% had symptoms at both time points (always group), 10% had late onset, and 24% had early onset of symptoms with remission. As compared with women in the never group, women in the always and late onset groups had high-risk characteristics (e.g., past history of depression), more situational triggers (e.g., physical symptoms), and less robust social and personal buffers (i.e., social support and self-efficacy). As compared with the never group, mothers in the remission group had more situational triggers and fewer buffers initially. Changes in situational triggers and buffers were different for the four groups and were correlated with group membership. Situational triggers such as physical symptoms and infant colic, and low levels of social support and self-efficacy in managing situational demands are associated with postpartum depressive symptoms. Further research is needed to investigate whether providing education about the physical consequences of childbirth, providing social support, and teaching skills to enhance self-efficacy will reduce the incidence of postpartum symptoms of depression.