Red blood cell distribution width (RDW) reflects erythrocyte size distribution, thus representing a reliable index of anisocytosis, widely used for the differential diagnosis of micro- and normocytic anaemias. Along with the large use in diagnostic hematology, RDW has been associated with presence and complications of a vast array of human pathologies during the last decades, including cardiovascular (CV) diseases. This article is hence aimed to provide an overview of important studies and systematic reviews with meta-analysis, in which RDW has been associated with CV events and mortality, in the attempt of establishing whether enough evidence exists for supporting its routine use in clinical practice. According to available data it seems reasonable to conclude that although the diagnostic specificity is low, and this measure is still plagued by important lack of standardization, RDW can be regarded as an index of enhanced patient fragility and higher vulnerability to adverse outcomes. Abnormal RDW values shall hence persuade physicians to broaden the diagnostic reasoning over anaemias, especially those due to malnutrition or malabsorption, encompassing a comprehensive assessment of traditional and non-traditional CV risk factors.