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Background Bone and mineral abnormalities, and cardiovascular calcification are associated with increased cardiovascular mortality in patients with chronic kidney disease (CKD). Recent studies have implicated Wnt signaling pathway in the pathogenesis of bone metabolism and vascular calcification. Sclerostin is a soluble inhibitor of Wnt signaling pathway and has been shown to be associated with decreased bone turnover and vascular calcification in CKD patients. Objectives The aim was to investigate whether the circulating levels of sclerostin are associated with all-cause mortality in prevalent hemodialysis patients. Methods Data are prospectively collected for 24 months for survival analysis in 350 prevalent hemodialysis patients. At baseline, serum sclerostin levels were measured and arteriovenous fistula calcification was detected by using a 64-detector computerized tomographic scanner. Results During the follow-up, 84 (24%) patients died. Patients who died had higher serum sclerostin levels. Kaplan–Meier curve revealed that patients with increasing tertiles of serum sclerostin levels at baseline, had a worse survival. In the multivariate Cox regression analysis age, albumin, and presence of arteriovenous fistula calcification, but not sclerostin levels, were found to be independent predictors of survival in maintenance hemodialysis patients. Conclusion Further clinical studies with longer follow-up are needed to clarify the impact of serum sclerostin levels on morbidity and mortality of maintenance hemodialysis patients. Clinical trial registration number The study was performed as a post hoc survival analysis of the patients involved in a single-center prospective trial investigating the association between serum sclerostin levels and arteriovenous fistula calcification and patency [Balci M, et al. Herz 2015;40:289–97] with a Clinicaltrials.gov number: NCT01382966 .