The clinical course of discrete subaortic stenosis (DSS) varies considerably between patients. This study was performed to identify echocardiographic characteristics of DSS that distinguish progressive from nonprogressive disease. The study included 100 patients from 2 institutions and was performed in 2 stages. In phase I, a prediction model was developed based on multivariate analysis of morphometric and Doppler variables obtained from the initial echocardiogram in 52 children with DSS from Texas Children's Hospital. In phase II, the performance characteristics of the prediction model were tested in 48 patients with DSS followed at Children's Hospital in Boston. Patients were divided into 3 outcome groups: nonprogressive, progressive, and intermediate progression. In phase I, multivariate analysis identified 3 independent predictors of progressive disease: indexed aortic valve to subaortic membrane distance, anterior mitral leaflet involvement, and initial Doppler gradient. The logistic regression equation--Probability = [1 + e-(-322+0.334X1+4.06X2-0.708X3)](-1), where X = initial gradient in mm Hg; X2 = absence (0) or presence (1) of mitral leaflet involvement; and X3 = indexed distance between aortic valve and subaortic membrane in mm/body surface area0.5 were used to predict progression. When the prediction model was applied to phase II study patients, none of the patients with nonprogressive DSS had a prediction value > 0.29 and none of the patients with progressive DSS had a prediction value < 0.58. Thus, a prediction value > 0.55 yielded a 100% sensitivity and 100% specificity for distinguishing progressive from nonprogressive DSS. Patients with intermediate progression were indistinguishable from progressive DSS but were clearly separable from nonprogressing patients. We conclude that progressive subaortic obstruction in children with DSS can be predicted from morphologic, morphometric, and Doppler echocardiographic analysis of left ventricular outflow.