Although helium-related fatalities and concerns about potentially harmful effects of helium use have increased in recent years, virtually nothing is known about the epidemiology of helium inhalation in adolescents. This exploratory investigation examined the prevalence and correlates of helium inhalation in a large sample of at-risk youth. Study participants were 723 Missouri adolescents (M age = 15.5, SD = 1.2) in residential treatment for delinquent behavior. More than one-in-nine (N = 81, 11.5%) adolescents had inhaled helium with the intention of getting high, and one-third (N = 27, 34.2%) of helium users reported they actually did get high when they inhaled helium. Helium users were significantly more likely to be Caucasian, to live in rural/small town areas, and to have histories of mental illness, auditory hallucinations, and alcohol and marijuana use than nonusers. Helium users also reported significantly more current psychiatric distress, suicidality, traumatic life experiences, and antisocial attitudes, traits, and behaviors than nonusers. Helium inhalation was prevalent in this sample and many such users reported getting high while using helium. Helium users had psychosocial profiles similar to those of volatile solvent users, suggesting that they may be at substantial risk for a variety of adverse health outcomes.