Many human diseases such as cancer, neurological diseases, autism and diabetes are associated with exposure to pesticides, especially organochlorine pesticides. However, pesticide exposure is also associated with cardiovascular disease (CVD) as the leading cause of death worldwide. In this systematic review, results on the link between organochlorine pesticide pollution and CVD were collected from databases (Medline (PubMed), Scopus and Science Direct) in May 2022 from studies published between 2010 and 2022. A total of 24 articles were selected for this systematic review. Sixteen articles were extracted by reviewers using a standardized form that included cross-sectional, cohort, and ecological studies that reported exposure to organochlorine pesticides in association with increased CVD risk. In addition, eight articles covering molecular mechanisms organochlorine pesticides and polychlorinated biphenyls (PCBs) on cardiovascular effects were retrieved for detailed evaluation. Based on the findings of the study, it seems elevated circulating levels of organochlorine pesticides and PCBs increase the risk of coronary heart disease, especially in early life exposure to these pesticides and especially in men. Changes in the regulatory function of peroxisome proliferator-activated γ receptor (PPARγ), reduction of paroxonase activity (PON1), epigenetic changes of histone through induction of reactive oxygen species, vascular endothelial inflammation with miR-expression 126 and miR-31, increased collagen synthesis enzymes in the extracellular matrix and left ventricular hypertrophy (LVH) and fibrosis are mechanisms by which PCBs increase the risk of CVD. According to this systematic review, organochlorine pesticide exposure is associated with increased risk of CVD and CVD mortality through the atherogenic and inflammatory molecular mechanism involving fatty acid and glucose metabolism.© 2023 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.