Stroke is one of the most common causes of disability and lack of independence in activities of daily living in adults. One of the most important factors predisposing to stroke, besides hypertension and atrial fibrillation, is carotid atherosclerosis. Rupture of unstable plaque with formation of a platelet plug is the cause of about 20-25% of ischemic strokes. Osteoprotegerin (OPG) is an important regulator of bone remodeling under physiological and disease conditions, as well as the regulator of osteoclast differentiation. Elevated plasma OPG level is associated with increased risk of ischemic stroke and heart diseases, including atrial fibrillation, and is observed in patients with symptomatic carotid artery stenosis and atherosclerotic vulnerable plaques. Furthermore, the occurrence of certain genotypes of OPG is 10 times more common in people with unstable atherosclerotic plaque, making them an independent risk predictor of plaque instability. This article summarizes the current state of knowledge on the potential role of OPG as a biomarker and prognostic indicator of stroke.