The red blood cell distribution width (RDW) is a rather simple measure of red blood cell (RBC) size heterogeneity (i.e., anisocytosis), which is easily calculated by dividing the standard deviation (SD) of erythrocyte volumes for the mean corpuscular volume (MCV). Emerging evidence suggests that, besides RBC abnormalities, many human disorders may be frequently associated with a high degree of anisocytosis.In this narrative review, we analyzed the current scientific literature about the putative role and the potential epidemiologic association between RDW and cardiovascular diseases. The findings of the most representative epidemiological studies were summarized and discussed.Overall, considerable and convincing evidence has been brought that an increased RDW value is associated with acute coronary syndrome (ACS) [including acute myocardial infarction (AMI)], ischemic cerebrovascular disease (including stroke), peripheral artery disease (PAD), as well as with atrial fibrillation (AF), heart failure (HF) and hypertension. Higher anisocytosis also significantly and independently predicts adverse outcomes in patients with these conditions.Although the role of anisocytosis in the pathogenesis of cardiovascular diseases remains uncertain, the considerable evidence available so far suggests that the clinical use of RDW may be broadened beyond the conventional boundaries of erythrocyte disorders, in particular for assisting the diagnosis and prognostication of patients with ACS, ischemic cerebrovascular disease, PAD, HF and AF.