Importance: Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.

Question: Which pharmacotherapies are associated with improved outcomes for people with alcohol use disorder?

Findings: In this systematic review and meta-analysis that included 118 clinical trials and 20 976 participants, 50 mg/d of oral naltrexone and acamprosate were each associated with significantly improved alcohol consumption-related outcomes compared with placebo.

Meaning: These findings support oral naltrexone at 50 mg/d and acamprosate as first-line therapies for alcohol use disorder.