BACKGROUND Low baroreflex sensitivity (BRS) indicates poor prognosis after acute myocardial infarction. Noninvasive BRS assessment is complicated by nonstationarities and noise in electrocardiogram and pressure signals. Phase-rectified signal averaging is a novel signal processing technology overcoming these problems. OBJECTIVE To prospectively validate a BRS measure (baroreflex sensitivity assessed by means of phase-rectified signal averaging [BRSPRSA]) based on this technology. METHODS Nine hundred forty-one consecutive acute myocardial infarction survivors aged 80 years or younger in sinus rhythm were prospectively enrolled at 2 German university hospitals. All patients underwent 30-minute recordings of electrocardiogram and arterial blood pressures (Portapres; TNO-TPD Biomedical Instrumentation, Amsterdam, Netherlands) within the first 2 weeks after myocardial infarction. BRSPRSA was prospectively dichotomized at 1.58 ms/mm Hg. Primary end point was all-cause mortality at 5 years. Multivariable analyses included Global Registry of Acute Coronary Events score (dichotomized at >= 120), sex, BRSPRSA, left ventricular ejection fraction (dichotomized at <= 35%), and diabetes mellitus. BRSPRSA was compared with 3 standard noninvasive BRS measures, that is, the sequence method, the transfer function method, and the correlation method. RESULTS During follow-up, 72 patients (7.7%) died. BRSPRSA stratified the study population into a high-risk group of 405 patients (<= 1.58 ms/mm Hg) with an estimated 5-year mortality of 14.2% and a low-risk group of 536 patients (>1.58 ms/mm Hg) with a 5-year mortality of 2.8% (P < .0001). On multivariable analysis, BRSPRSA <= 1.58 ms/mm Hg was associated with a hazard ratio of 3.1 (confidence interval 1.7-5.6; P = .001). Predictive power of BRSPRSA <= 1.58 ms/mm Hg was particularly strong in patients with a Global Registry of Acute Coronary Events score of >= 120 or with a left ventricular ejection fraction of <= 35%. CONCLUSION BRSPRSA is a powerful and independent predictor of mortality in postinfarction patients especially when assessed in patients with a Global Registry of Acute Coronary Events score of >= 120 or a left ventricular ejection fraction of <= 35%.