Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is known to be among the mediators of the calcification process that has been shown to increase in patients with aortic stenosis (AS). The aim of this study was to characterize the association of OPG with left ventricular (LV) function and remodeling and to evaluate the significance of preoperative OPG on long-term outcome in terms of survival and symptomatic improvement in 124 patients with severe AS scheduled for aortic valve replacement (AVR). Patients were divided according to tertiles of preoperative OPG. Preoperative OPG was associated with age, EuroSCORE, and preoperative functional capacity. Despite similar ejection fraction and diastolic function among groups, longitudinal LV systolic function consistently decreased and markers of filling pressure increased across groups. During median follow-up of 4 years, 41 patients died of a presumed cardiovascular cause or remained in New York Heart Association functional class III or IV. The risk of a poor postoperative outcome after AVR increased with increasing OPG tertiles (15% vs 33% vs 51%, p = 0.002). In a multivariate model containing age, ejection fraction, N-terminal pro-brain natriuretic peptide and left atrial volume index, OPG was still significantly associated with postoperative outcome. In addition, OPG levels associated with cardiovascular mortality during follow-up. In conclusion, OPG is associated with LV and left atrial remodeling in patients with symptomatic severe AS undergoing AVR. Moreover, plasma OPG is associated with long-term postoperative outcome and may identify patients with poor symptomatic improvement after surgery.