This study sought to evaluate the relation between 12-lead ventricular tachycardia (VT) electrocardiography (ECG) and VT-related anatomical isthmuses (AIs) in repaired tetralogy of Fallot (rTOF). Slow-conducting AIs are the dominant VT substrate in rTOF. Whether an AI is considered critical relies on pace mapping (PM) guided by the VT ECG. VT ECGs, electroanatomical mapping data and PM results were analyzed in 25 rTOF patients (group 1) (age 57 ± 13 years). Selection of PM and ablation sites was guided by VT ECG. In 7 patients (group 2) (age 33 ± 14 years), PM was systematically performed within all AIs, irrespective of the VT ECG. In group 1, all 35 induced VTs (median VT cycle length 270 [interquartile range: 240 to 310] ms) were AI related. All 11 right bundle branch block (RBBB) VTs were related to AI3 (right ventricular septum if positive concordant [7 of 7]), coronary cusp if V2 transition break [3 of 4]). Left bundle branch block (LBBB) VTs with transition <V5 were mapped to AI3 (8 of 10) or AI2 (2 of 10) and LBBB VTs with transition ≥V5 to AI1 (8 of 14), AI3 (5 of 14), and AI4 (1 of 14). In group 2, all 8 induced VTs (median VT cycle length 240 [interquartile range: 230 to 268] ms) were AI related. All RBBB VTs were related to AI3 (right ventricular septum). For LBBB VTs, paced matches were obtained in AI3 and AI1. Activation mapping and/or ablation success confirmed AI3 to be critical for all 8 VTs. In rTOF with only AI1 and AI3, RBBB VTs are due to clockwise and LBBB VTs to counterclockwise activation of AI3. Involvement of both AIs in the VT circuit limits the role of the 12-lead VT ECG and PM. AI3 can always be targeted irrespective of the 12-lead VT ECG.