Background and AimsOpioid-related overdose is increasingly linked to pregnancy-associated deaths, but factors associated with postpartum overdose are unknown. We aimed to estimate the strength of the association between maternal and infant characteristics and postpartum opioid-related overdose. Design Retrospective cohort study using a linked, population-level data set. Setting Massachusetts, United States. Conclusion Among women who delivered live infants in Massachusetts, USA between 2012 and 2014, maternal diagnosis of OUD, prior non-fatal overdose, infant diagnosis of NAS and high unscheduled health-care utilization appeared to be positively associated with postpartum opioid overdose. However, more than half of postpartum overdoses in that period were to women without a diagnosis of OUD. Engagement in methadone or buprenorphine treatment in the month prior to delivery was not sufficient to reduce the odds of postpartum overdose. Participants Women who delivered one or more live births from 2012 to 2014 (n = 174 517). Measurements The primary outcome was opioid-related overdose in the postpartum year. We used multivariable logistic regression to explore the independent associations of maternal (demographics, substance use, pregnancy) and infant [gestational age, birthweight, neonatal abstinence syndrome (NAS)] characteristics with postpartum opioid overdose. Findings were stratified by maternal opioid use disorder (OUD) diagnosis. Findings There were 189 deliveries to women who experienced ≥ 1 opioid overdose in the first year postpartum (11 of 10 000 deliveries). Among women with postpartum opioid overdose, 46.6% had an OUD diagnosis within 12 months before delivery. In our adjusted model, maternal diagnosis of OUD [adjusted odds ratio (aOR) = 3.61, 95% confidence interval (CI) = 1.73-7.51] and prior non-fatal overdose (aOR = 2.40, 95% CI = 1.11-5.17) were most strongly associated with postpartum overdose. After stratifying by OUD status, infant diagnosis of NAS (OUD + aOR = 2.03, 95% CI = 1.26-3.27; OUD -aOR = 2.79, 95% CI = 1.12-6.93) and high unscheduled health-care utilization (OUD + aOR = 2.27, 95% CI = 1.38-3.73; OUD -aOR = 2.11, 95% CI = 1.24-3.58) were positively associated with postpartum overdose in both groups. 90% of substance use-related pregnancy-associated deaths occurred after 6 weeks postpartum, compared with 60% of all other pregnancy-associated deaths [1][2][3][4][5]. In Massachusetts, the 7-12 months following delivery were