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Background and Objectives: Laws liberalizing access to medical marijuana are associated with reduced opioid analgesic use among adults, but little is known about the impact of such policies on adolescents and young adults. Methods: This retrospective cohort study used 2005 to 2014 claims from MarketScan® Commercial database, which covers all 50 states and Washington D.C. The sample included 195,204 adolescent and young adult patients (aged 12–25) who underwent one of 13 surgical procedures. Results: Of the 195,204 patients, 4.8% had prolonged opioid use. Several factors were associated with a higher likelihood of prolonged opioid use, including being female (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.21–1.33), longer hospital stay (aOR, 1.04; 95% CI, 1.02–1.06), greater days of index opioid supply (8–14 days: aOR, 1.39, 95% CI, 1.33–1.45; greater than 14 days: aOR, 2.42, 95% CI, 2.26–2.59), rural residence (aOR, 1.07; 95% CI, 1.01–1.14), and cholecystectomy (aOR, 1.16; 95% CI, 1.08–1.25). There was not a significant association of medical marijuana dispensary laws on prolonged opioid use (aOR, 0.98; 95% CI, 0.81–1.18). Conclusions and Scientific Significance: Medical marijuana has been suggested as a substitute for opioids, but our results focusing on adolescents and young adults provide new evidence that this particularly vulnerable population does not exhibit reductions in prolonged use of opioids after surgery when they have legal access to medical marijuana. These findings are the first to demonstrate potentially important age differences in sustained use of opioids, and point to the need for prescriber oversight and management with this vulnerable population. [ABSTRACT FROM AUTHOR]