BACKGROUND: Produce prescriptions may improve cardiometabolic health by increasing fruit and vegetable (F&V) consumption and food insecurity yet impacts on clinical outcomes and health status have not been evaluated in large, multisite evaluations. METHODS: This multisite, pre- and post-evaluation used individual-level data from 22 produce prescription locations in 12 US states from 2014 to 2020. No programs were previously evaluated. The study included 3881 individuals (2064 adults aged 18+ years and 1817 children aged 2–17 years) with, or at risk for, poor cardiometabolic health recruited from clinics serving low-income neighborhoods. Programs provided financial incentives to purchase F&V at grocery stores or farmers markets (median, $63/months; duration, 4–10 months). Surveys assessed F&V intake, food security, and self-reported health; glycated hemoglobin, blood pressure, body mass index (BMI), and BMI z -score were measured at clinics. Adjusted, multilevel mixed models accounted for clustering by program. RESULTS: After a median participation of 6.0 months, F&V intake increased by 0.85 (95% CI, 0.68–1.02) and 0.26 (95% CI, 0.06–0.45) cups per day among adults and children, respectively. The odds of being food insecure dropped by one-third (odds ratio, 0.63 [0.52–0.76]) and odds of improving 1 level in self-reported health status increased for adults (odds ratio, 1.62 [1.30–2.02]) and children (odds ratio, 2.37 [1.70–3.31]). Among adults with glycated hemoglobin ≥6.5%, glycated hemoglobin declined by −0.29% age points (−0.42 to −0.16); among adults with hypertension, systolic and diastolic blood pressures declined by −8.38 mm Hg (−10.13 to −6.62) and −4.94 mm Hg (−5.96 to −3.92); and among adults with overweight or obesity, BMI decreased by −0.36 kg/m ² (−0.64 to −0.09). Child BMI z -score did not change −0.01 (−0.06 to 0.04). CONCLUSIONS: In this large, multisite evaluation, produce prescriptions were associated with significant improvements in F&V intake, food security, and health status for adults and children, and clinically relevant improvements in glycated hemoglobin, blood pressure, and BMI for adults with poor cardiometabolic health.