Accurate evaluation of the appearance of QTc sex differences during childhood and adolescence is intricate. Inter-subject differences of individual QT/RR patterns make generic heart rate corrections inaccurate because of fast resting heart rates in children. The study investigated 527 healthy children and adolescents aged 4 to 19 years (268 females, 50.9%). All underwent continuous ECG 12-lead monitoring while performing postural changes during a 70-minute investigative protocol to obtain QT interval measurements at different heart rates. On average, more than 1200 ECG measurements (QT interval and its 5-minute history of preceding RR intervals) were made in each subject. Curvilinear QT/RR regression involving intra-individual correction for QT/RR hysteresis were calculated in each subject. The projection of the QT/RR regressions to the heart rate of 60 beats per minute defined individually corrected QTc intervals. In males, gradual QTc shortening by about 15 ms appeared during the ages of 13-19 years and appeared synchronously with the incidence of secondary sex signs (p=0.016). On the contrary, whilst gradual QTc prolongation by about 10 ms appeared in females, it occurred only during ages 16-19 years and was not related to the incidence of secondary sex signs (p=0.18). The study also showed that in children and adolescents, linear QT/RR models fit the intra-subject data significantly more closely than the log-linear models (p<0.001). The study speculates that hormonal shifts during puberty might be directly responsible for the QTc shortening in males but that QTc prolongation in females is likely more complex since it was noted to follow the appearance of secondary sex signs only after a considerable delay.