We compared the effectiveness of physician-directed clinical decision support (CDS) administered via electronic health record (EHR) vs. patient-directed education to promote appropriate use of opioids by conducting a cluster-randomized trial involving 82 primary care physicians and 951 of their patients with chronic pain. Primary outcomes were satisfaction with patient-physician communication (CG-CAHPS) and pain interference (PROMIS®). Secondary outcomes included physical function (PROMIS®), depression (PHQ-9), high-risk opioid prescribing (>90 morphine milligram equivalents per day [≥90 MME/day]), and co-prescription of opioids and benzodiazepines. We used multi-level regression to compare longitudinal difference-in-difference scores between arms. The odds of achieving the maximum CG-CAHPS score was 2.65 times higher in the patient education vs. CDS arm (P=.044; 95% CI 1.03-6.80). However, baseline CG-CAHPS scores were dissimilar between arms, making these results challenging to interpret definitively. No difference in pain interference was found between groups (Coef=-0.64, 95% CI -2.66-1.38). The patient education arm experienced higher odds of Rx≥90 MME/day (OR=1.63; P=.010; 95% CI 1.13,2.36). There were no differences between groups in physical function, depression, or co-prescription of opioids and benzodiazepines. These results suggest that patient-directed education may have potential to improve satisfaction with patient-physician communication, whereas physician-directed CDS via EHR may have greater potential to reduce high-risk opioid dosing. More evidence is needed to ascertain relative cost-effectiveness between strategies. PERSPECTIVE: This article presents the results of a comparative-effectiveness study of two broadly used communication strategies to catalyze dialogue between patients and PCPs around chronic pain. The results add to the decision-making literature and offer insights about the relative benefits of physician-directed vs. patient-directed interventions to promote appropriate use of opioids.Copyright © 2023. Published by Elsevier Inc.