Purpose <p>Both adult and pediatric studies have shown that patients who receive opioid analgesics for acute postsurgical pain can develop prolonged opioid use after surgery (POUS). We performed a systematic review to synthesize the rates of POUS in children, adolescents, and young adults from existing literature, and to identify associated risk factors.</p> Methods <p>We searched the databases of MEDLINE, Embase, and CINAHL to identify studies examining the rate of POUS in pediatric and young adult participants. Studies were included if they 1) were prospective or retrospective observational studies investigating the rate of prolonged postoperative opioid use, 2) included patients undergoing any type of surgical procedures, and 3) included pediatric or young adult participants. We assessed the risk of bias in included studies using an adapted version of the Scottish Intercollegiate Guideline Network checklist for cohort studies. Using a best-evidence synthesis, we assessed risk factors based on criteria including the number of studies investigating it, the quality of studies, and the consistency of the association.</p> Results <p>In this systematic review of 17 studies including 1,576,515 participants, the estimated median reported rate of POUS in children, adolescents, and young adults was 4.5%. Older age, female sex, history of chronic pain, and preoperative opioid use were patient-level risk factors associated with development of POUS.</p> Conclusion <p>We identified four patient-level predictors of POUS in this systematic review. Clinicians should attempt to identify patients with risk factors preoperatively and devise strategies to mitigate the risk for development of POUS.</p> Study registration <p>PROSPERO (<a href="https://www.crd.york.ac.uk/PROSPERO/view/295977">CRD42022295977</a>); first submitted 6 December 2021.</p>