Best biomarker of Vitamin D status is calcifediol. We investigated the relationship between serum calcifediol levels and vertebral fractures (VF), vascular calcifications (VC) and mortality in hemodialysis patients. Cross-sectional study in 18 hospital based dialysis centers in Italy, we included 387 hemodialysis patients (143 F, 37% ; 244 M, 63%), mean age 64±14 (SD) years, median dialytic age 49 months, BMI 25± 4 Kg/m2. We evaluated VF with a computerized analysis of scanned L-L vertebral X-rays (T4 to L5). Reduction of > 20% of vertebral body height was considered a VF, while reductions between 15% and 20% were considered borderline fractures (BF). VC assessments were also centralized. Witteman’s method was used for blinded assessments in duplicate. VC were quantified by measuring the length of calcific deposits along wall of the aorta and iliac arteries. Follow up was 2.7±0.5 years. Bone markers were: Ca 9.15±0.68 mg/dl, P 4.8± 1.28 mg/dl, median ALP 83 U/L and median PTH 244 pg/ml. We found a median 25(OH)D level of 28.9 ng/ml. Nine ( 2.3%) patients had vitamin D deficiency (<10 ng/ml), 198 ( 51.2%) patients had vitamin D insufficiency (between 10-29.9 ng/ml) and 180 (46.5%) patients had normal levels ( >30 ng/ml). We found that 55% of patients had VF and 30.9% of patients had BF. Prevalence of VC was 80.6% in the aorta and 55,1% in the iliac arteries. Males had more VF than Females (60% versus 48%, P=0.019). No associations were found between VF and biochemical parameters including calcifediol levels (p=0.662), while we found an association between low calcifediol levels and a higher prevalence of severe aortic calcifications (36.8 vs 28.2, p=0.0044). Furthermore, we found a OR 1.85 (1.04-3.29 CI, p=0.0367) for Aortic Calcification in patients with calcifediol levels lower than the median value of 29 ng/ml. During follow-up (2.7±0.5 years) mortality was of 19.9%. Our study suggests that high calcifediol levels could be protective against progression of severe aortic calcification.