Most pregnancy-related deaths due to mental health conditions, which include overdose and poisoning related to substance use disorder, occur during the late (43-365-day) postpartum period (1). Adverse childhood experiences and stressful life events are associated with increased substance use during pregnancy (2,3). Pregnancy Risk Assessment Monitoring System (PRAMS) respondents in seven states with high opioid overdose mortality rates were recontacted 9-10 months after giving birth in 2019 and asked about postpartum prescription opioid misuse,* tobacco use, unhealthy alcohol use,† and use of other substances.§ Substance and polysubstance use prevalence estimates were calculated, stratified by mental health and social adversity indicators. Overall, 25.6% of respondents reported postpartum substance use, and 5.9% reported polysubstance use. The following conditions were associated with higher substance and polysubstance use prevalence in postpartum women: depressive symptoms, depression, anxiety, adverse childhood experiences, and stressful life events. Substance use prevalence was higher among women who experienced six or more stressful life events during the year preceding the birth (67.1%) or four adverse childhood experiences related to household dysfunction (57.9%). One in five respondents who experienced six or more stressful life events in the year before giving birth and 26.3% of women with four adverse childhood experiences reported postpartum polysubstance use. Clinical and community- and systems-level interventions to improve postpartum health can include screening and treatment for depression, anxiety, and substance use disorders during the postpartum period. Evidence-based strategies can prevent adverse childhood experiences and mitigate the immediate and long-term harms.¶.