Objective Opioid abuse and overdose constitute an ongoing health emergency. Many presume opioids have little potential for iatrogenic addiction when used as directed, particularly in short courses as is typical of the ED setting. We preliminarily explored the possibility that initial exposure to opioids by EDs could be related to subsequent opioid misuse. Methods This cross-sectional study surveyed a convenience sample of patients reporting heroin or non-medical opioid use at an urban, academic ED. We estimated the proportion whose initial exposure to opioids was a legitimate medical prescription and the proportion of those prescriptions that came from an ED. Secondary measurements included 1) the proportion using non-opioid substances before initial opioid exposure, 2) the source of opioids between initial exposure and onset of regular non-medical use, and 3) time from initial prescription to opioid use disorder. Results Of 59 subjects, 35 (59%; 95%CI: 47-71) reported they were first exposed to opioids by a legitimate medical prescription, and for 10/35 (29%; 95%CI: 16-45), the prescription came from an ED. Most medically exposed subjects (28/35, 80%; 95%CI: 65-91) reported non-opioid substance use or treatment for non-opioid substance use disorders preceding the initial opioid exposure. Emergency providers were a source of opioids between exposure and onset of regular non-medical use in 11/35 (31%, 95%CI: 18-48) cases. Thirty-one of the 35 medically exposed subjects reported the time of onset of non-medical use; median time from exposure to onset of non-medical use was: 6 months for use to get high (N=25; IQR 2-36), 12 months for regular use to get high (N=24, IQR: 2-36), 18 months for use to avoid withdrawal (N=26, IQR: 2-38), and 24 months for regular use to avoid withdrawal (N=27, IQR: 2-48). Eleven (36%, 95%CI: 21-53) began non-medical use within 2 months, and 9/11 (82%, 95%CI: 53-96) reported non-opioid substance use or treatment for alcohol abuse prior to initial opioid exposure. Conclusion Although short-term opioid administration by emergency providers is unlikely to cause addiction by itself, ED opioid prescriptions may contribute to the development of addiction in some patients. There is an urgent need for further research to estimate long-term risks of short-course opioid therapy, so that the risk of iatrogenic addiction can be appropriately balanced with the benefit of analgesia.