Objectives This study sought to develop a novel automated technique, simultaneous amplitude frequency electrogram transformation (SAFE-T), to identify ventricular tachycardia (VT) isthmuses by analysis of sinus rhythm arrhythmogenic potentials (AP). Background Substrate ablation is useful for patients with scar-related hemodynamically unstable VT; however, the accuracy of different approaches remains inadequate, varying from targeting late potentials to full scar homogenization. Methods High-density ventricular mapping was performed in 3 groups: 1) 18 normal heart control subjects; 2) 10 ischemic patients; and 3) 8 nonischemic VT patients. In VT patients, isthmus sites were characterized using entrainment responses. Sinus rhythm right ventricle/left ventricle endocardial and epicardial electrograms underwent Hilbert-Huang spectral analysis and were displayed as 3-dimensional SAFE-T maps. AP and their relation to the VT isthmus sites were studied. Results AP were defined by a cutoff value of 3.08 Hz mV using normal heart control subjects. Receiver-operating characteristics showed that VT isthmus sites were best identified using SAFE-T mapping (p < 0.001) as compared with bipolar and unipolar scar and late potential mapping with an optimal cutoff value of 3.09 Hz mV, allowing identification of 100% of the 34 mapped VT isthmuses, compared with 68% using late potentials. There was no significant difference between sinus rhythm and paced SAFE-T values. Abnormal SAFE-T areas involved about one-quarter of the scar total area. Conclusions Automated electrogram analysis using 3-dimensional SAFE-T mapping allows rapid and objective identification of AP that reliably detect VT isthmuses. The results suggest that SAFE-T mapping is good alternative strategy to late potential mapping in identifying VT isthmuses and allows reduced ablation as compared to scar homogenization.