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Prescription drug monitoring programs (PDMPs) are a crucial component of federal and state governments’ response to the opioid epidemic. Evidence about the effectiveness of PDMPs in reducing prescription opioid–related adverse outcomes is mixed. We conducted a systematic review to examine whether PDMP implementation within the United States is associated with changes in 4 prescription opioid–related outcome domains: opioid prescribing behaviors, opioid diversion and supply, opioid-related morbidity and substance-use disorders, and opioid-related deaths. We searched for eligible publications in Embase, Google Scholar, MEDLINE, and Web of Science. A total of 29 studies, published between 2009 and 2019, met the inclusion criteria. Of the 16 studies examining PDMPs and prescribing behaviors, 11 found that implementing PDMPs reduced prescribing behaviors. All 3 studies on opioid …