Mitral annular calcification (MAC) is a common echocardiographic finding and an increasingly recognized cause of degenerative mitral stenosis (DMS). However, little is known about the clinical characteristics and disease progression in DMS, particularly in comparison with rheumatic mitral stenosis (RMS). We retrospectively reviewed 203 consecutive patients with mitral stenosis (113 with DMS and 90 with RMS) who underwent echocardiography at our institution between January 2014 and December 2017. We compared the clinical characteristics and disease progression between the 2 groups. In addition, we analyzed the predictors of disease progression (defined as annual progression rate of a mean gradient >0 mm Hg/year) among patients with DMS. Patients with DMS were significantly older and had higher prevalence of atherosclerotic comorbidities than those with RMS. During the median follow-up period of 2.2 years, the annual progression rates were comparable (0.8 ± 0.8 mm Hg/year in DMS vs 1.0 ± 1.2 mm Hg/year in RMS; p = 0.32) and were highly variable (0.0 to 3.5 mm Hg/year in DMS and 0.0 to 5.5 mm Hg/year in RMS) within both groups among disease progression. In DMS patients, atherosclerotic comorbidities and lower initial mean gradient were significantly associated with disease progression even after adjustment by age and sex. There was no significant difference in the disease progression according to the circumferential MAC severity determined by echocardiography among DMS. In conclusion, DMS disease progression was slow but highly variable, similar to that of RMS. In patients with DMS, the baseline MAC severity did not correlate with disease progression, suggesting the importance of follow-up echocardiography regardless of the MAC severity.