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Importance: Unhealthy alcohol use (UAU) is the fourth most preventable cause of death in the US. The US Preventive Services Task Force recommends that primary care clinicians routinely screen all adults 18 years and older for UAU; however, this preventive service is poorly implemented., Objective: To determine if practice facilitation improved delivery of the recommended care for UAU compared to usual care., Design, Setting, and Participants: This practice-level cluster randomized clinical trial was conducted across diverse and representative primary care practices throughout Virginia. A total of 76 primary care practices enrolled between October 2019 and January 2023., Intervention: Practices received immediate (intervention) or 6-month delayed (control) practice facilitation, which included tailored educational sessions, workflow management, and tools for addressing UAU., Main Outcomes and Measures: Outcomes included the increase in recommended screening for UAU, brief interventions, referral for counseling, and medication treatment. Data were collected via medical record review (structured and free text data) and transcripts of practice facilitator sessions and exits interviews., Results: Of the 76 primary care practices enrolled, 32 were randomized to intervention and 35 to control; 11 789 patients (mean [SD] age, 50.1 [16.3] years; 61.1% women) were randomly selected for analysis, with patient demographics similar to Virginia at large. From baseline to 6 months after intervention, screening with a validated instrument increased from 2.1% (95% CI, 0.5%-8.4%) to 35.5% (95% CI, 11.5%-69.9%) in the intervention group compared to 0.4% (95% CI, 0.1%-1.8%) to 1.4% (95% CI, 0.3%-5.8%) in the control group (P < .001). Brief office-based interventions for the intervention group increased from 26.2% (95% CI, 14.2%-45.8%) to 62.6% (95% CI, 43.6%-78.3%) vs 45.5% (95% CI, 28.0%-64.1%) to 55.1% (95% CI, 36.5%-72.3%) in the control group (P = .008). Identification of UAU, referral for counseling, and medication treatment had similar changes for both groups. Qualitative analyses of transcripts revealed that few clinicians understood the preventive service prior to practice facilitation, but at the end most felt much more competent and confident with screening and brief intervention for UAU., Conclusions and Relevance: This cluster randomized clinical trial demonstrated that practice facilitation can help primary care practices to better implement screening and counseling for UAU into their routine workflow. Effective primary care practice implementation interventions such as this can have a profound effect on the health of communities. Given the number of people that the participating practices care for, this intervention resulted in an additional 114 604 patients being screened annually for UAU who would not have been otherwise., Trial Registration: ClinicalTrials.gov Identifier: NCT04248023.