Mitral annular calcium (MAC) is a common finding at echocardiography, although it is an unusual cause of severe mitral stenosis. Although MAC is known to be associated with atherosclerosis and chronic kidney disease, little is known about its natural history as affects mitral valve function. This report describes a cohort of 37 outpatients with severe MAC (>5 mm) of whom 32 were followed longitudinally with echocardiography (mean follow-up 2.6 ± 1.6 years). Progression of the mitral valve gradient occurred in 16 of 32 (50%). There was wide variation in rate of progression with a few subjects demonstrating a rapid increase in gradient, up to 9 mm Hg/year. Progression of mitral valve gradient correlated with baseline gradient at rest and with severity of overall cardiac calcification as measured by a semiquantitative echocardiographic score. Age at index echocardiogram was inversely related to mitral valve gradient after baseline, suggesting that calcification may proceed at a greater rate in younger patients. In conclusion, although severe mitral stenosis is uncommon in patients with MAC, those with a pre-existing gradient at rest and severe overall cardiac calcification appear to be at greater risk for development of this disease state.