Background The Tpeak-end(Tp-e) has not been compared in all 12 ECG leads in healthy adults to determine if the Tp-e varies across leads. If there is variation, it remains uncertain which lead(s) are preferred for recording in order to capture the maximal Tp-e value. The purpose of the current study was to determine the optimal leads, if any, to capture the maximal Tp-e interval in healthy young adults. Methods In 88 healthy adults(ages 21-38 years), including derivation(n=21), validation(n=20), and smoker/vaper(n=47) cohorts, the Tp-e was measured using commercial computer software (LabChart Pro8 with ECG module, ADInstruments) in all 12 leads at rest and following a provocative maneuver, abrupt standing. Tp-e was compared to determine which lead(s) most frequently captured the maximal Tp-e interval. Results In the rest and abrupt standing positions, the Tp-e was not uniform among the 12 leads; the maximal Tp-e was most frequently captured in the precordial leads. At rest, grouping leads V2-V4 resulted in detection of the maximum Tp-e in 85.7% of participants(CI 70.7, 99.9%) vs all other leads (p<0.001). Upon abrupt standing, grouping leads V2-V6 together, resulted in detection of the maximum Tp-e in 85.0% of participants (CI 69.4, 99.9% vs all other leads; p<0.001). These findings were confirmed in the validation cohort, and extended to the smoking/vaping cohort. Conclusion If only a subset of ECG leads will be recorded or analyzed for the Tp-e interval, selection of the precordial leads is preferred since these leads are most likely to capture the maximal Tp-e value.