Electrocardiographic measures can facilitate the identification of patients at risk of death after acute coronary syndromes. This study evaluates a new risk metric, morphologic variability (MV), which measures beat-to-beat variability in the shape of the entire heart beat signal. This metric is analogous to heart rate variability (HRV) approaches, which focus on beat-to-beat changes in the heart rate. MV was calculated using a dynamic time-warping technique in 764 patients from the DISPERSE2 (TIMI 33) trial for whom 24-hour continuous electrocardiograph was recorded within 48 hours of non-ST-elevation acute coronary syndrome. The patients were evaluated during a 90-day follow-up for the end point of death. Patients with high MV showed an increased risk of death during follow-up (hazard ratio 8.46; p <0.001). The relationship between high MV and death could be observed even after adjusting for baseline clinical characteristics and HRV measures (adjusted hazard ratio 6.91; p = 0.001). Moreover, the correlation between MV and HRV was low (R < or =0.25). These findings were consistent among several subgroups, including patients under the age of 65 and those with no history of diabetes or hyperlipidemia. In conclusion, our results suggest that increased variation in the entire heart beat morphology is associated with a considerably elevated risk of death and may provide information complementary to the analysis of heart rate.