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In recent years, epidemiological monitoring data has indicated sharp increases in prescription drug misuse. Despite these increases, little is known about the context or patterns associated with prescription drug misuse, particularly among youth or young injection drug users (IDUs). A three-city study of 213 young IDUs found prescription drug misuse to be pervasive, specifically the use of opioids and benzodiazepines. Particular practices not commonly associated with prescription drugs were reported, such as sniffing, smoking, and injection. Associated health risks included initiation into injection drug use, polydrug use, drug overdose, and drug dependency. A greater awareness of the potential health risks associated with prescription drug misuse should be incorporated into services that target IDUs, including street outreach, syringe exchanges, and drug treatment.