BACKGROUND: The need for accurate risk stratification is heightened by the expanding indications for the implantable cardioverter defibrillator. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) focused interest on patients with both depressed left ventricular ejection fraction (LVEF) and the presence of nonsustained ventricular tachycardia (NSVT). Meanwhile, the prospective study Autonomic Tone and Reflexes After Myocardial Infarctio (ATRAMI) demonstrated that markers of reduced vagal activity, such as depressed baroreflex sensitivity (BRS) an heart rate variability (HRV), are strong predictors of cardiac mortality after myocardial infarction. METHODS AND RESULTS: We analyzed 1071 ATRAMI patients after myocardial infarction who had data on LVEF, 24-hour ECG recording, and BRS. During follow-up (21 +/- 8 months), 43 patients experienced cardiac death, 5 patients had episodes of sustained VT, and 30 patients experienced sudden death and/or sustained VT. NSVT, depressed BRS, or HRV were all significantly and independently associated with increased mortality. The combination of all 3 risk factor increased the risk of death by 22x. Among patients with LVEF<35%, despite the absence of NSVT, depressed BRS predicted higher mortality (18% versus 4.6%, P = 0.01). This is a clinically important finding because this grou constitutes 25% of all patients with depressed LVEF. For both cardiac and arrhythmic mortality, the sensitivity of lo BRS was higher than that of NSVT and HRV CONCLUSIONS: BRS and HRV contribute importantly and additionally to risk stratification. Particularly when LVEF is depressed, the analysis of BRS identifies a large number of patients at high risk for cardiac and arrhythmic mortalit who might benefit from implantable cardioverter defibrillator therapy without disproportionately increasing the number of false-positives.