BACKGROUND: Policy support for "food is medicine"-medically tailored meals or groceries to improve health-is rapidly growing. No randomized trials have heretofore investigated the benefits of medically tailored food programs for people with human immunodeficiency virus (PWH). METHODS: The CHEFS-HIV pragmatic randomized trial included PWH who were clients of Project Open Hand (POH), a San Francisco-based nonprofit food organization. The intervention arm (n = 93) received comprehensive medically tailored meals, groceries, and nutritional education. Control participants (n = 98) received less intensive (POH "standard of care") food services. Health, nutrition, and behavioral outcomes were assessed at baseline and 6 months later. Primary outcomes measured were viral nonsuppression and health-related quality of life. Mixed models estimated treatment effects as differences-in-differences between arms. RESULTS: The intervention arm had lower odds of hospitalization (odds ratio [OR], 0.11), food insecurity (OR, 0.23), depressive symptoms (OR, 0.32), antiretroviral therapy adherence <
90% (OR, 0.18), and unprotected sex (OR, 0.18), as well as less fatty food consumption (β = -.170 servings/day) over 6 months, compared to the control arm. There was no difference between study arms in viral nonsuppression and health-related quality of life over 6 months. CONCLUSIONS: A "food is medicine" intervention reduced hospitalizations and improved mental and physical health among PWH, despite no impact on viral suppression. CLINICAL TRIALS REGISTRATION: NCT03191253.