Aims: The aim of the present study is to elucidate the optimal lead to be selected for the evaluation of drug-induced QT prolongation. Methods and Results: We assessed the validity of each electrocardiography (ECG) lead for the evaluation of QT intervals in 688 patients receiving psychotropic drugs. Abnormal QTc prolongation was observed in 96 (14%) patients using the longest ECG lead. Prevalence of QTc prolongation was larger when using leads I, III, aVR, aVL, aVF, V1, and V6 (>18%), and smaller when using lead V2 (10%). In the remaining 4 ECG leads, the overall accuracy to predict QTc prolongation was higher when using lead V3 (94%) compared with lead II (89%) or lead V5 (90%). Sensitivity to predict QTc prolongation was higher when using lead V4 (81%) compared with lead II (66%) or lead V2 (63%). Conclusion: When a single lead was used for the evaluation of QT prolongation, the results were not always similar to those using the lead which demonstrated the longest QT interval, and if only one lead is to be chosen, lead V3 or V4 should be selected.