To determine if the signal-averaged (SA) electrocardiogram (ECG) predicts the occurrence of sustained ventricular arrhythmia and sudden death after acute myocardial infarction, 182 consecutive patients underwent systematic noninvasive testing, including the SAECG. Seventy-one patients (39%) had an abnormal SAECG. The presence of an abnormal SAECG was not related to underlying left ventricular dysfunction or any other clinical or measured variable. There were 16 end points (sustained ventricular arrhythmia or sudden cardiac death) during 14-month follow-up. The SAECG was a significant predictor of these events (p less than 0.02), and an abnormal SAECG conferred a 2.7-fold increase in risk. The risk associated with an abnormal SAECG was independent of both left ventricular function and ventricular arrhythmia on Holter ECG. The SAECG had excellent negative predictive accuracy (95%), but the positive predictive accuracy was low (15%). When the results of the SAECG were combined with the results of the Holter ECG, a group of very high-risk patients was identified; at 18 months, the presence of abnormal SAECG and Holter ECG was associated with a risk of 26% compared with only 4% if both tests were normal. Furthermore, all published studies with a similar design were pooled for meta-analysis. The meta-analysis revealed a sixfold increase in risk, independent of left ventricular function, and an eightfold increase in risk, independent of Holter results when the SAECG was abnormal. The SAECG is a noninvasive test that can rapidly and easily provide potent prognostic information regarding the risk of sustained ventricular arrhythmias for patients after myocardial infarction.