BACKGROUND In response to the national epidemic of prescription opioid misuse and related adverse outcomes, two clinical pharmacists developed a telephone risk assessment clinic to promote safe opioid prescribing through a monthly assessment of patient medication use, aberrant behaviors, and side effects. METHODS A pilot group of five primary care providers and their patients with chronic nonmalignant pain on chronic opioid therapy, defined as having received prescription opioid medications for ≥90 days in the last 120 days, were identified. A risk assessment evaluation based on Veterans Health Administration/Department of Defense Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain was created. Factors assessed were receipt of non-San Francisco Veterans Administration Health Care System controlled substance prescriptions through California's prescription drug monitoring program, urine drug test (UDT) results, and aberrant behaviors. Pharmacist-recommended changes to regimen and provider response to recommendation were compiled. The pilot was conducted from December 15, 2014, to March 31, 2015. RESULTS Among 608 patients on chronic opioid therapy, 148 were assigned to pilot providers and 447 assessments were completed. Twenty-five (16.8%) patients had non-VA controlled substance prescriptions, of which 14 (56.0%) patients filled a non-VA controlled substance within 3 months of the start of pilot. Seventeen UDT results inconsistent with their prescribed regimens were identified from 12 patients (8.1%). Pharmacists recommended 66 changes to chronic opioid prescriptions in 48 patients (32.4%), including decreasing quantity of opioid(s) (33.3%), discontinuing chronic opioid therapy (22.7%), and delaying a fill (19.7%). Sixty-one of 66 (92.5%) pharmacist recommendations for regimen change were implemented by providers. Chronic opioid therapy was discontinued in 14 (9.5%) patients over the course of the pilot study. CONCLUSIONS A pharmacist-led telephone risk assessment clinic improved adherence to clinical guidelines and changed opioid prescribing practices in more than one third of assessed patients.