OBJECTIVES: To assess the content validity and patient interpretation of the Prescription Opioid Misuse and Abuse Questionnaire (POMAQ), a questionnaire to evaluate potential prescription opioid misuse and abuse behaviors among patients with chronic pain prescribed long-term opioid therapy, as part of FDA PMR Study 3033-3. METHODS:  A cross-sectional, qualitative study was conducted in patients with chronic pain, most currently on prescription opioids. Four patient groups were recruited from 6 clinical sites (Known Opioid Abusers; Known Abusers of Other Substances; Non-opioid Abusers; and Non-opioid Users) to participate in a one-on-one cognitive interview. Patients completed the POMAQ via web-administration and participated in an in-depth semi-structured interview to assess the patient’s understanding of the questionnaire. Descriptive statistics and content analysis were performed. RESULTS:  54 patients were interviewed. Mean age was 48.7 ± 12.3 years; 57.1% female; 78.6% Caucasian; mean duration of chronic pain was 11.2 ± 8.2 years with lower back pain at 74.5%. Overall, the POMAQ was well-understood, received positive feedback, and all but one participant stated they were comfortable completing the questionnaire. A few (n=6, 11%) expressed concerns about completing the POMAQ using a secure internet site as they were not computer savvy (n=3, 5.4%) or were concerned about internet security (n=3, 5.4%). All participants stated they were honest when completing the POMAQ, but 51% (n=18/35) did not think others would be honest when completing the POMAQ. Minor wording modifications were made to the POMAQ to address concerns or issues noted by the participants and to enhance clarity and understanding of the POMAQ. CONCLUSIONS:  The POMAQ has demonstrated acceptability and content validity among patients with chronic pain. The POMAQ is currently undergoing quantitative validation among a larger cohort of chronic pain patients on prescription opioids.