The prognostic value of stress echocardiography to predict future cardiac events using the extent and severity of wall motion abnormalities is not well defined. The objective of this study was to develop and validate a prognostic model for interpretation of stress echocardiographic studies by using the extent and severity of wall motion abnormalities. We evaluated 1,500 patients (59 +/- 13 years old; 51% men) who underwent stress echocardiography (34% on the treadmill exercise and 66% on dobutamine). Left ventricular regional wall motion was assessed by consensus of 2 experienced echocardiographers. Follow-up periods (mean 2.7 +/- 1.0 years) for confirmed myocardial infarction (n = 31) and cardiac death (n = 44) were identified. Multivariate regression analysis identified 2 independent predictors of cardiac events: the number of left ventricular wall segments with new wall motion abnormalities (an index of the extent of ischemia) and the maximal magnitude of new wall motion abnormalities (an index of the severity of ischemia). The ischemic extent (chi-square 48.7, p <0.0001) and maximal severity (chi-square 52.0, p <0.0001) were exponentially correlated with an increase in event rate. On the basis of these data, a prognostic model was defined that uses ischemic extent and maximal severity as stress-dependent orthogonal variables. With this 3-dimensional model, the predicted event rate ranged over sevenfold, from a low of 0.9%/year in patients without any wall motion abnormalities to a high of 6.7%/year in patients with extensive and severe wall motion abnormalities. The extent and severity of wall motion abnormalities by stress echocardiography are independent and cumulative predictors of prognosis in patients who have suspected or known ischemic heart disease.