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As opioid use-related behaviors continue at epidemic proportions, identifying the root causes of these behaviors is critical. Adverse childhood experiences (ACEs) are shown to be an important predictor of opioid initiation, opioid dependence, and lifetime opioid overdose. The purpose of this systematic review is to examine the association between ACEs and opioid use-related behaviors later in life and to discuss implications for policy, practice, and research regarding ACEs and opioids. Five databases (PubMed, PsycINFO, CINAHL, Medline, and Scopus) were used to identify studies investigating the association between ACEs and opioid use-related behaviors. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 20 studies out of the initial 428 met the inclusion criteria for this review. Among the included 20 studies, 15 focused on the relationship between ACEs and lifetime opioid use-related behaviors, and five focused on current opioid use-related behaviors. All studies found statistical associations between ACEs and lifetime or current opioid use-related behaviors. Five studies found a significant gradient effect; that is, as the number of ACEs increased, the risk of opioid use-related behaviors also increased. A significant dose–response relationship exists between ACEs and opioid use-related behaviors. Hence, it is essential for clinicians to screen for ACEs before prescribing opioid medications, for opioid treatment to incorporate trauma-informed methods, and for messaging around opioid use interventions to include information about ACEs. The current review points to a critical need to implement standardized ACE screening instruments in clinical and research settings. [ABSTRACT FROM AUTHOR]