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Background and aims Between 2007 and 2016, pregnancy-associated mortality resulting from overdose more than doubled in the United States. This study explored the circumstances surrounding maternal opioid-related morbidity and mortality, using the life-course theory as a sensitizing framework to examine how each participant's life-course contributed to her substance use, relapse, recovery or overdose. Design A mixed-methods study using semi-structured, in-depth face-to-face interviews and focus groups were conducted. Setting Texas, United States. Participants Women who had relapsed into opioid use or experienced a 'near-miss' overdose and family members of women who had died during the maternal period due to opioid overdose were interviewed (n = 99). Measurements A socio-demographic questionnaire captured participants' ethnicity, age, marital status, medical and mental health history and employment status. The Stressful Life Events Screening Questionnaire-revised (SLESQ-R) assessed life-time exposure to trauma. Findings Women reported histories of abuse and loss of a loved one through homicide or suicide. Participants indicated that limited social support, interpersonal conflict with their partner and unaddressed mental illness made recovery more challenging. Additionally, losing their children through the child welfare system was described as punitive and placed them at greater risk for relapse and overdose. Conclusions A life-course theory approach to examining maternal opioid-related morbidity and mortality in Texas, United States reveals the complex needs of women at risk for opioid use relapse and overdose and the significant role of previous traumatic experiences.