BACKGROUND: Although left ventricular ejection fraction (LVEF) is the primary determinant for sudden cardiac death (SCD) risk stratification, in isolation, LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker strategy would provide more robust SCD risk stratification than LVEF alone. METHODS: We collected patient-level data (n = 3355) from 6 studies assessing the prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of the group was used for derivation (n = 2242) and one-third for validation (n = 1113). The discriminative capacity of the multivariable model was assessed using the area under the receiver-operating characteristic curve (c-index). The primary endpoint was SCD at 24 months. RESULTS: In the derivation cohort, 59 patients experienced SCD by 24 months. Stepwise selection suggested that a model based on 3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD risk prediction. In the derivation cohort, the c-index of the model was 0.817, which was significantly better than LVEF used as a single variable (0.637, P < .001). In the validation cohort, 36 patients experienced SCD by 24 months. The c-index of the model for predicting the primary endpoint was again significantly better than LVEF alone (0.774 vs 0.671, P = .020). CONCLUSIONS: A multivariable model based on presence of coronary artery disease, LVEF and MTWA status provides significantly more robust SCD risk prediction than LVEF as a single risk marker. These findings suggest that multi-marker strategies based on different aspects of the electro-anatomic substrate may be capable of improving primary prevention implantable cardioverter-defibrillator treatment algorithms.