Recent data have shown that exercise electrocardiogram (ECG) has no incremental prognostic value over clinical and rest ECG parameters in chest pain patients without a history of coronary artery disease (CAD). The incremental prognostic value of stress echocardiography (SE) in this population is unknown. Accordingly, 547 consecutive patients (68 ± 4.9 years) with chest pain but no previous history of CAD, referred for SE (exercise and dobutamine), were identified. Patients were followed up for death and acute myocardial infarction (AMI). At a median follow-up period of 28 months, there were a total of 35 hard cardiac events (5 deaths and 30 non-fatal AMI). Among the prognostic clinical, resting/stress ECG, and SE data, univariate predictors were the Framingham risk score (P = 0.025), diabetes (P = 0.06), hypercholesterolaemia (P = 0.06), stress ECG ischaemia (P = 0.044), stress heart rate (P = 0.019), and SE-determined ischaemic burden (stress-rest wall thickening score index; P < 0.001). In a multivariate model, ischaemic burden was the only independent predictor of events (P < 0.001). SE also showed incremental prognostic value over and above clinical (Framingham's risk score) and stress ECG changes in a global χ(2) model. This was true also for patients undergoing only exercise SE (n = 347). SE provides both independent and incremental prognostic value for the prediction of hard cardiac events in chest pain patients without a previous history of CAD-over and above clinical, ECG, and stress ECG data.