Background: Clinician utilization of practice guidelines can reduce inappropriate opioid prescribing and harm in chronic non-cancer pain; yet, implementation of “opioid guidelines” is subpar. We hypothesized that a multi-component quality improvement (QI) augmentation of “routine” system-level implementation efforts would increase clinician adherence to the opioid guideline-driven policy recommendations. Methods: Opioid policy was implemented system-wide in 26 primary care clinics. A convenience sample of 9 clinics received the QI augmentation (one-hour academic detailing; 2 online educational modules; 4-6 monthly one-hour practice facilitation sessions) in this non-randomized stepped-wedge QI project. The QI participants were volunteer clinic staff. The target patient population was adults with chronic non-cancer pain treated with long-term opioids. The outcomes included the clinic-level percentage of target patients with a current treatment agreement (primary outcome), rates of opioid-benzodiazepine co-prescribing, urine drug testing, depression and opioid misuse screening, and prescription drug monitoring database check; additional measures included daily morphine-equivalent dose (MED), and the percentages of all target patients and patients prescribed ≥90mg/day MED. T-test, mixed-regression and stepped-wedge-based analyses evaluated the QI impact, with significance and effect size assessed with two-tailed p<0.05, 95% confidence intervals and/or Cohen’s d. Results: Two-hundred-fifteen QI participants, a subset of clinical staff, received at least one QI component; 1,255 patients in the QI and 1,632 patients in the 17 comparison clinics were prescribed long-term opioids. At baseline, more QI than comparison clinic patients were screened for depression (8.1% vs 1.1%, p=0.019) and prescribed ≥90mg/day MED (23.0% vs 15.5%, p=0.038). The stepped-wedge analysis did not show statistically significant change in outcomes in the QI clinics, when accounting for the comparison clinics’ trends. The Cohen’s d values favored the QI clinics in all outcomes except opioid-benzodiazepine co-prescribing. Subgroup analysis showed that patients prescribed ≥90mg/day MED in the QI compared to comparison clinics improved urine drug screening rates (38.8% vs 19.1%, p=0.02), but not other outcomes (p³0.05). Conclusions: Augmenting routine policy implementation with targeted QI intervention, delivered to volunteer clinic staff, did not additionally improve clinic-level, opioid guideline-concordant care metrics. However, the observed effect sizes suggested this approach may be effective, especially in higher-risk patients, if broadly implemented.Trial Registration – Not applicable