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Objective: Mitral annular calcification (MAC) is associated with systemic calcification and cardiovascular disease (CVD) events. Matrix Gla protein (MGP) is a strong inhibitor of vascular and soft-tissue calcification and reduced levels of its circulating precursor, uncarboxylated MGP (ucMGP), was found associated with vascular calcification in pilot studies. Methods and Results: In this study, which includes 86 outpatients with no significant coronary artery and chronic kidney diseases, we measured serum ucMGP levels and evaluated MAC using echocardiography. In participants with MAC (n = 44), serum ucMGP levels were lower than the control group (n = 42) (216.1 ± 154.1 vs. 390.2 ± 256.3, P = 0.001, respectively). The patients with MAC were divided into two groups: mild MAC group and moderate MAC group. Serum ucMGP levels were significantly lower in the moderate MAC group than the mild MAC group (139.0 ± 121.8 vs. 248.4 ± 156.3, P = 0.03, respectively). Conclusions: In patients with MAC, serum ucMGP level was significantly low, and this association has been detected for the first time in patients with no significant coronary artery disease (CAD).