Despite an alarming recent increase in prescription opioid abuse, the characteristics of prescription opioid abusers remain largely unknown. In this study, the demographic and drug use characteristics of 75 methadone patients (36 prescription opioid and 39 heroin users) were compared using a retrospective chart review. Prescription opioid abusers exhibited a profile of characteristics that may predict favorable treatment response, including less severe opioid use and IV drug use, and greater social stability compared to primary heroin abusers. Despite the limitations inherent in this retrospective chart review, this study provides initial evidence that prescription opioid abusers may have a number of characteristics that predict favorable treatment response. This new information may inform and assist current efforts to develop efficacious treatments for prescription opioid abuse.