Outcomes from produce prescription (PPR) programs, an exemplar of a Food is Medicine intervention, have not been synthesized. The objective of this study was to conduct a systematic review to examine the impact of PPR programs on food security, fruit and vegetable (FV) intake, and/or cardiovascular risk factors (HbA1c, blood pressure, and blood lipids). Searches were conducted across three databases (PubMed, CINAHL, and Web of Science). Eligible studies were published between August 2012 and April 2023, conducted in the US in child/family, or adult populations, written in English and had a PPR program as an exposure. Food security, FV intake, and/or cardiovascular risk factors. Twenty studies ranging from a duration of between 6 weeks to 24 months were included. Of the 5 studies (3 in child/family and 4 in adult populations) that analyzed changes in food security status, all reported significant (P < 0.05) improvements after the PPR program. Approximately half of the included studies found significant (P < 0.05) increases in fruit, vegetable, and/or FV intake. Only studies in adult populations included cardiovascular risk factor outcomes. In these studies, mixed findings were reported; however, there were significant (P < 0.05) improvements in HbA1c when PPR programs enrolled individuals with type 2 diabetes. PPR programs provide an opportunity to improve food security in child/family, and adult populations. Evidence to support whether PPR programs increase FV intake and improve cardiovascular disease risk factors outside of HbA1c in adult populations with high HbA1c upon enrollment is less known.