Chronic pain patients who show aberrant drug-related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was to conduct a randomized trial in patients who were prescribed opioids for noncancer back pain and who showed risk potential for or demonstration of opioid misuse to see if close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids. Forty-two patients meeting criteria for high-risk for opioid misuse were randomized to either standard control (High-Risk Control; N=21) or experimental compliance treatment consisting of monthly urine screens, compliance checklists, and individual and group motivational counseling (High-Risk Experimental; N=21). Twenty patients who met criteria indicating low potential for misuse were recruited to a low-risk control group (Low-Risk Control). Patients were followed for 6 months and completed pre- and post-study questionnaires and monthly electronic diaries. Outcomes consisted of the percent with a positive Drug Misuse Index (DMI), which was a composite score of self-reported drug misuse (Prescription Drug Use Questionnaire), physician-reported abuse behavior (Addiction Behavior Checklist), and abnormal urine toxicology results. Significant differences were found between groups with 73.7% of the High-Risk Control patients demonstrating positive scores on the DMI compared with 26.3% from the High-Risk Experimental group and 25.0% from the Low-Risk Controls (p<0.05). The results of this study demonstrate support for the benefits of a brief behavioral intervention in the management of opioid compliance among chronic back pain patient at high-risk for prescription opioid misuse.