Background: These studies were carried out to examine whether the onset and progression of an opioid substance use disorder (SUD) differed in those who first used opioids to get "high" compared to those who received a prescription from a doctor to relieve pain (Non-Rx vs. Rx groups, respectively). Methods: A subset of patients (N = 214) from an ongoing larger study of patients entering one of 125 drug treatment programs for opioid use disorder across the country agreed to give up their anonymity and participate in structured and open-ended online interviews examining drug abuse patterns. Results: With the exception that the Non-Rx group began their opioid abuse at a younger age than the Rx group and more quickly evolved from initial exposure to regular opioid abuse, there were relatively few differences in the characteristics, patterns and trajectories of opioid abuse. The vast majority of patients in both groups, most of whom had serious, antecedent psychiatric disorders, indicated that they used opioids to self-medicate psychological problems (67-73%) and/or stated that opioids provided a means to "escape" from the stresses of everyday life (79-85%). As the SUD progressed, for many individuals any "positive" attributes of opioids waned and avoidance of withdrawal became the overriding concern, often serving as the impetus for treatment. Conclusions: Our results suggest that self-treatment of co-morbid psychiatric disturbances is a powerful motivating force to initiate and sustain abuse of opioids and that the initial source of drugs a prescription or experimentation is largely irrelevant in the progression to a SUD. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.