Objectives. Using two-dimensional echocardiography, we sought to identify features that are associated with severe mitral regurgitation after percutaneous mitral valvulotomy and combine them into a predictive score. Background. Severe mitral regurgitation after percutaneous mitral valvulotomy is a major complication carrying an adverse prognosis that, to date, has not been predictable in advance. Methods. In a consecutive series of 566 patients who underwent percutaneous mitral valvulotomy, 37 (6.5%) developed severe mitral regurgitation (assessed by angiography) after the procedure, 31 of whom had an echocardiogram available before percutaneous mitral valvulotomy. These 31 patients were matched by age, gender, mitral valve area and degree of mitral regurgitation before valvulotomy with 31 randomly selected patients who did not develop severe mitral regurgitation after percutaneous mitral valvulotomy. An echocardiographic score was developed on the basis of the pathologic studies of valves of patients who developed severe regurgitation after percutaneous mitral valvulotomy (leaflet rupture of relatively thin portions of nonhomogeneously thickened leaflets in the presence of commissural and subvalvular calcification) and evaluated uneven distribution of thickness in the anterior and posterior mitral leaflets, degree of commissural disease and subvalvular disease involvement, with each component graded from 0 to 4 (total, 0 to 16). Intraobserver and interobserver variability for score assessment were 6% and 7%, respectively. Results. The total mitral regurgitation echocardiographic score was significantly greater in the severe mitral regurgitation group (11.7 ± 1.9 [mean ± SD] vs. 8.0 ± 1.2, p < 0.001). In addition, the component grades for the anterior leaflet (3.2 ± 0.7 vs. 2.3 ± 0.6, p < 0.001), commissures (2.6 ± 0.7 vs. 1.6 ± 0.6, p < 0.001) and subvalvular apparatus (3.2 ± 0.6 vs. 2.3 ± 0.7, p < 0.001) were also higher in the mitral regurgitation group. With a total score ≥ 10 as a cutoff point for predicting severe mitral regurgitation after percutaneous mitral valvulotomy, a sensitivity of 90 ± 5% and a specificity of 97 ± 3% were obtained. Stepwise logistic regression analysis identified the mitral regurgitation echocardiographic score as the only independent predictor for developing severe mitral regurgitation after percutaneous mitral valvulotomy (p < 0.0001). Conclusions. This new mitral regurgitation echocardiographic score can predict the development of severe mitral regurgitation after percutaneous mitral valvulotomy and can be useful in the selection of patients for this technique.