BACKGROUND: Plant-based diets are gaining attention globally due to their environmental benefits and perceived health-protective role. A vegan diet may have cardiovascular benefits; however, evidence remains conflicting and insufficiently assessed. OBJECTIVES: We evaluated the utility of the vegan diet in cardiovascular disease (CVD) prevention. METHODS: We conducted a systematic review of studies evaluating the association between vegan diets and cardiovascular outcomes. We searched 5 databases (Ovid MEDLINE, EMBASE, Web of Science, Scopus, and OpenGrey) through 31 October 2020. Four investigators independently screened the full texts for inclusion, assessed quality, and extracted data from published reports. RESULTS: Out of the 5729 identified records, 7 were included, comprising over 73,000 participants, of whom at least 7661 were vegans. Three studies, with at least 73,426 individuals (including at least 7380 vegans), examined risks of primary cardiovascular events (total CVD, coronary heart disease, acute myocardial infarction, total stroke, hemorrhagic stroke, and ischemic stroke) in individuals who followed a vegan diet compared to those who did not. None of the studies reported a significantly increased or decreased risk of any cardiovascular outcome. One study suggested that vegans were at greater risk of ischemic stroke compared to individuals who consumed animal products (HR, 1.54; 95% CI, 0.95-2.48). Yet in another study, vegans showed lower common carotid artery intima-media thickness (0.56 ± 0.1 mm vs. 0.74 ± 0.1 mm in controls; P < 0.001), and in 3 studies of recurrent CVD events, vegans had 0-52% lower rates. Furthermore, endothelial function did not differ between vegans and nonvegans. Using the Grading of Recommendations Assessment, Development and Evaluation approach, evidence was deemed to be of low to very low strength/quality. CONCLUSIONS: Among the Western populations studied, evidence weakly demonstrates associations between vegan diets and risk of CVDs, with the direction of associations varying with the specific CVD outcome tested. However, more high-quality research on this topic is needed. This study was registered at PROSPERO as CRD42019146835.