Background: Vascular calcification (VC) represents one of the major complications associated with progressive renal impairment. Matrix Gla-protein (MGP) is a vitamin Kdependent protein that acts as a powerful inhibitor of vascular calcification. Despite this fact, it remains unknown whether supplementation with vitamin K can lead to reduction or reversal of vascular and heart valve calcification. Our study aims primarily to investigate the effect of oral vitamin K1 three times weekly for a total duration of 6 months on the serum levels of dephosphorylated-uncarboxylated MGP (dp-ucMGP) as well as aortic calcification score and severity of aortic and mitral valve lesions. As secondary objectives, we investigated the association between hyperphosphatemia or dialysis duration and the radiologic aortic calcification or the severity of aortic and mitral valve lesions. Methods: One hundred and twenty end-stage kidney disease (ESKD) patients on regular HD for > 6months with a high level of Serum dp-ucMGP were enrolled and were supplemented with 5 mg of vitamin K1 3 times /week for 6 months after each HD session. Serum dp-ucMGP, echocardiography, Plain lateral abdominal x-ray were performed before and 6 months after vitamin K1 supplementation. Results: We found a significant difference in the baseline dp-ucMGP (pM) in relation to severity of aortic or mitral valve lesions at baseline (p <0.001; p = 0.001, respectively), so that severe aortic and mitral valve lesions were associated with higher dpucMGP levels. Compared with baseline levels, serum dp-ucMGP was about 8 times lower after supplementation with vitamin K1 for 6 months (p<0.001). Despite this decrease, we found no significant change in the radiologic aortic calcification score (p = 0.083), or the severity of aortic and mitral valve lesions compared to the baseline evaluation (p=0.059 and 0.083, respectively). Conclusion: our findings suggest that hemodialysis patients show increased serum levels of dp-ucMGP which might occur subsequent to the progressive vascular and heart valvular calcification. Although vitamin K supplementation in hemodialysis patients leads to activation of dp-ucMGP into pcMGP, this might not be sufficient on the short run to drive a significant reduction in aortic calcification score or in the severity of aortic or mitral valve lesions. Keywords: Vitamin K, ESRD, Vascular calcification, Hemod