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The effectiveness of this approach for prescription opioids among patients with chronic noncancer pain remains untested.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To evaluate the effectiveness of a government-led educational information brochure mailed to community-dwelling, long-term opioid consumers to reduce prescription opioid use compared with usual care.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cluster randomized clinical trial was conducted from July 2018 to January 2019 in Manitoba, Canada. All adults with long-term opioid prescriptions were enrolled (n\u2009=\u20094225). Participants were identified via the Manitoba Drug Program Information Network. Individuals receiving palliative care or with a diagnosis of cancer or dementia were excluded. Data were analyzed from July 2019 to March 2020.<\/jats:p><\/jats:sec>Intervention<\/jats:title>Participants were clustered according to their primary care clinic and randomized to the intervention (a codesigned direct-to-consumer educational brochure sent by mail) or usual care (comparator group).<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The main outcome was discontinuation of opioid prescriptions at the participant level after 6 months, ascertained by pharmacy drug claims. Secondary outcomes included dose reduction (in morphine milligram equivalents [MME]) and\/or therapeutic switch. Reduction in opioid use was assessed using generalized estimating equations to account for clustering, with prespecified subgroup analyses by age and sex. Analysis was intention to treat.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 4206 participants, 2409 (57.3%) were male; mean (SD) age was 60.0 (14.4) years. Mean (SD) baseline opioid use was comparable between groups (intervention, 157.7 [179.7] MME\/d; control, 153.4 [181.8] MME\/d). After 6 months, 235 of 2136 participants (11.0%) in 127 clusters in the intervention group no longer filled opioid prescriptions compared with 228 of 2070 (11.0%) in 124 clusters in the comparator group (difference, 0.0%; 95% CI, \u22121.9% to 1.9%). More participants in the intervention group than in the control group reduced their dose (1410 [66.0%] vs 1307 [63.1%]; difference, 2.8% [95% CI, 0.0%-5.7%]). Receipt of the brochure led to greater dose reductions for participants who were male (difference, 3.9%; 95% CI, 0.1%-7.7%), aged 18 to 64 years (difference, 3.7%; 95% CI, 0.2%-7.2%), or living in urban areas (difference, 5.9%; 95% CI, 1.9%-9.9%) compared with usual care.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this cluster randomized clinical trial, no significant difference in the prevalence of opioid cessation was observed after 6 months between the intervention and usual care groups; however, the intervention resulted in more adults reducing their opioid dose compared with usual care.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: 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