Rates of opioid prescribing tripled in the USA between 1999 and 2015 and were associated with significant increases in opioid misuse and overdose death. Roughly half of all opioids are prescribed in primary care. Although clinical guidelines describe recommended opioid prescribing practices, implementing these guidelines in a way that balances safety and effectiveness vs. risk remains a challenge. The literature offers little help about which implementation strategies work best in different clinical settings or how strategies could be tailored to optimize their effectiveness in different contexts. Systems consultation consists of (1) educational/engagement meetings with audit and feedback reports, (2) practice facilitation, and (3) prescriber peer consulting. The study is designed to discover the most cost-effective sequence and combination of strategies for improving opioid prescribing practices in diverse primary care clinics.