BackgroundVascular calcification (VC) is a complex process that has been linked to conditions including cardiovascular diseases and chronic kidney disease. There is an ongoing debate about whether vitamin K (VK) can effectively prevent VC. To assess the efficiency and safety of VK supplementation in the therapies of VC, we performed a systematic review and meta-analysis of recent studies.MethodsWe searched major databases, including PubMed, the Cochrane Library, Embase databases, and Web of Science up until August 2022. 14 randomized controlled trials (RCTs) describing the outcomes of treatment for VK supplementation with VC have been included out of 332 studies. The results were reported in the change of coronary artery calcification (CAC) scores, other artery and valve calcification, vascular stiffness, and dephospho-uncarboxylated matrix Gla protein (dp-ucMGP). The reports of severe adverse events were recorded and analyzed.ResultsWe reviewed 14 RCTs, comprising a total of 1,533 patients. Our analysis revealed that VK supplementation has a significant effect on CAC scores, slowing down the progression of CAC [I2= 34%, MD= −17.37, 95% CI (−34.18, −0.56),p= 0.04]. The study found that VK supplementation had a significant impact on dp-ucMGP levels, as compared to the control group, where those receiving VK supplementation had lower values [I2= 71%, MD = −243.31, 95% CI (−366.08, −120.53),p= 0.0001]. Additionally, there was no significant difference in the adverse events between the groups [I2= 31%, RR = 0.92, 95% CI (−0.79,1.07),p= 0.29].ConclusionVK may have therapeutic potential for alleviating VC, especially CAC. However, more rigorously designed RCTs are required to verify the benefits and efficacy of VK therapy in VC.