Context: Opioid-related harms continue to rise for children and youth. Analgesic prescribing decisions are challenging because the risk for future nonmedical opioid use or disorder is unclear.

Objective: To synthesize research examining the association between short-term therapeutic opioid exposure and future nonmedical opioid use or opioid use disorder and associated risk factors.

Data sources: We searched 11 electronic databases.

Study selection: Two reviewers screened studies. Studies were included if: they were published in English or French, participants had short-term (≤14 days) or an unknown duration of therapeutic exposure to opioids before 18 years, and reported opioid use disorder or misuse.

Data extraction: Data were extracted, and methodologic quality was assessed by 2 reviewers. Data were summarized narratively.

Results: We included 21 observational studies (49 944 602 participants). One study demonstrated that short-term therapeutic exposure may be associated with opioid abuse; 4 showed an association between medical and nonmedical opioid use without specifying duration of exposure. Other studies reported on prevalence or incidence of nonmedical use after medical exposure to opioids. Risk factors were contradictory and remain unclear.

Limitations: Most studies did not specify duration of exposure and were of low methodologic quality, and participants might not have been opioid naïve.

Conclusions: Some studies suggest an association between lifetime therapeutic opioid use and nonmedical opioid use. Given the lack of clear evidence regarding short-term therapeutic exposure, health care providers should carefully evaluate pain management options and educate patients and caregivers about safe, judicious, and appropriate use of opioids and potential signs of misuse.