Red blood cell distribution width (RDW) is a measure of red blood cell volume variations (anisocytosis) and is reported as part of a standard complete blood count. In recent years, numerous studies have noted the importance of RDW as a predictor of poor clinical outcomes in the settings of various diseases, including coronary artery disease (CAD). In this paper, we discuss the prognostic value of RDW in CAD and describe the pathophysiological connection between RDW and acute coronary syndrome. In our opinion, the negative prognostic effects of elevated RDW levels may be attributed to the adverse effects of independent risk factors such as inflammation, oxidative stress, and vitamin D3 and iron deficiency on bone marrow function (erythropoiesis). Elevated RDW values may reflect the intensity of these phenomena and their unfavorable impacts on bone marrow erythropoiesis. Furthermore, decreased red blood cell deformability among patients with higher RDW values impairs blood flow through the microcirculation, resulting in the diminution of oxygen supply at the tissue level, particularly among patients suffering from myocardial infarction treated with urgent revascularization.