Objective and Design. Individuals seeking treatment for chronic pain in multidisciplinary pain management services are typically already on high doses of pain medications. This cross-sectional cohort study of patients with long-term chronic pain examined profiles of polypharmacy and pain medication-related harm exposure. Setting. Multidisciplinary pain management service. Subjects. The cohort comprised 224 patients taking medications for their pain (1?9 medications; mean = 3.19) with an average pain duration of 10.33 years. Methods. The Medication Quantification Scale III (MQS-III) was used to examine potential harm exposure. We generated detriment scores for simple analgesics, adjunctive therapies (e.g., anticonvulsants), opioids, and benzodiazepines. Results. The total MQS-III score was correlated with the total number of medications, but not with age. Almost 10 of patients took medications from all four categories, with most taking medications from two (37 ) to three (35 ) classes. Eighty percent of patients were taking opioids, accounting for 41 of total MQS scores. Five primary profiles of potential medication-related harms were identified: high harm from all medication categories (N = 12); above average harm from single category?simple analgesics (N = 76), adjunctive analgesics (N = 59), or opioids (N = 46); and above average opioid and benzodiazepine harm (N = 31). Conclusions. While treatment with multiple medications for synergistic or adjunctive effects may assist in medical management of chronic pain, this approach generates increased potential harm exposure. We show that the majority of detriment comes from medications other than opioids and highlight the importance of profiling all pain medications contributing to polypharmacy in clinical pain studies.