This study examined the motives for medical misuse of prescription opioids among adolescents and assessed differences in motives by demographic characteristics, substance abuse, and diversion behaviors. A survey was conducted in 2011 to 2012 and the sample consisted of 2,964 adolescents (51% female). Thirteen percent reported past-year medical use of prescription opioids. Among those prescribed opioids in the past year (n = 393), 17.9% reported medical misuse (eg, using too much, using to get high, or using to increase alcohol or other drug effects). The most prevalent motives for medical misuse were ?to relieve pain? (84.2%) and ?to get high? (35.1%). Multivariate analyses indicated that the motives differed by race, and that different motives were associated with different substance abuse and diversion behaviors. The odds of past-year substance abuse among medical misusers motivated by non?pain relief were more than 15 times greater than for nonusers (adjusted odds ratio = 15.2, 95% CI = 6.4?36.2, P < .001). No such differences existed between nonusers and appropriate medical users, or between nonusers and medical misusers motivated by pain relief only. These findings improve our understanding of opioid medication misuse among adolescents and indicate the need for enhanced education about appropriate medical use, pain management, and patient communication with prescribers.