Background The current dietary recommendations for cardiovascular disease (CVD) risk reduction include increased fruit and vegetable consumption. The Opuntia spp., Prickly Pear (PP) fruit is rich in dietary fiber and may have lipid-lowering effects but it is often confused with the PP stem/leaf (Cladode (CLD)), or not identified. The efficacy of the PP fruit and CLD in reducing CVD risk is a growing area of research. Methods This systematic review (PROSPERO: CRD42018110643), examined the effects of consuming the Opuntia spp. components (PP or CLD) on CVD risk factors, specifically total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). The review, performed from February through September 2019, used resources available through Food Science and Technology Abstracts (EBSCO), Medline, Scopus, CINAHL, Web of Science and Cochrane databases. Results and Discussion Eleven articles met the inclusion criteria, which characterised Opuntia spp. products as either PP (n = 6), CLD (n = 5) or commercial products’ (n=1). Effects were investigated in healthy and obese populations as well as those with metabolic illnesses, specifically type 2 diabetes and metabolic syndrome. PP consumption was associated with significant reductions in TC (p < 0.05) in all but one included study, whereas in the remaining studies (n=6), LDL-C levels decreased (p < 0.05). Separately, the effect of CLD consumption on lipids was small with one study reporting a significant increase in plasma HDL-C in a subgroup of participants (>45 years of age) following consumption of a patented CLD powder product. It is plausible, that differences in overall effect may be due to compositional distinctions between CLD and PP, such as fiber composition. Care must be taken in future studies to accurately report the identity of the selected components of Opuntia spp.