Objective: We examine role of ACEs and pathways to risk of opioid misuse among young adults. Participants and Methods: A cross-sectional survey of validated measures of ACEs, risk of opioid misuse, and health conditions with a sample of 1,402 students from a large public university followed by multivariate logistic regression and pathway analysis. Results: Majority (61%) of participants reported at least one ACE. A dose-response relationship between numbers of ACEs with risk for opioid misuse was present. Compared to participants with no ACEs, participants with [greater than or equal to]4 ACEs and 0-3 ACEs were 2.93 (95% CI: 1.95, 4.39; p < 0.001) and 1.96 (95% CI: 1.46, 2.65; p < 0.001) times more likely to be at risk for opioid misuse, respectively. Having at least one existing or past health condition significantly mediated the association. Conclusions: Our findings suggest need to include assessment of ACEs as a screening criterion for opioid prescription and administration among college-aged individuals.