Introduction: Despite a marked increase in the abuse of prescription opioids over the past decade, relatively little is known about the characteristics of these abusers, and whether subtypes exist based on factors such as preferred route of abuse. Methods: We conducted a secondary analysis of the Treatment Episode Data Set (TEDS), a national-level, de-identified data set on admissions to substance abuse treatment facilities receiving public funding. Results: In 2005,1,849,548 admissions for treatment of alcohol and drug abuse were reported to TEDS. Opioid analgesics were reported as the primary drug of abuse in 3.7% of admissions, compared to 13.8% reporting heroin. Among the opioid analgesic abusers, 71.8% preferred the oral route; 13.1% preferred inhaling; 12.2%, injecting; 1.9%, smoking; and 0.9%, “other.” Those who preferred abusing opioid analgesics by inhaling, injecting, or smoking were more likely to report having first abused these drugs prior to age 25 (73.9%, 68.5%, and 66.4%, respectively) as compared to those who preferred oral abuse (53.2%). Injectors were less likely to be employed (22.7%) than inhalers (30.3%), smokers (29.8%), or oral abusers (29.6%). A higher percentage of both injectors and oral abusers reported psychiatric problems (29.0%) as compared to inhalers (26.1%), or smokers (17.5%). Injectors were also more likely to report abusing cocaine/crack cocaine as a secondary or tertiary drug of abuse (25.4%) compared to inhalers (20.2%), smokers (15.5%), or oral abusers (14.8%). Inhalers and oral abusers were more likely to abuse opioid analgesics daily (64.5% and 65.0%, respectively) than those who abused via injecting (56.2%) or smoking (53.4%). Conclusions: Subtyping abusers of opioid analgesics by preferred route of abuse reveals important differences in socio-demographic, health-related, and substance abuse characteristics.