A prolonged heart rate corrected QT interval (QTc) increases the risk of sudden cardiac death. Some methods of heart rate correction (notably Bazett) overestimate QTc in people with high heart rates. Studies suggest that tricyclic antidepressants (TCAs) can prolong the QTc and increase heart rate. Therefore, we aimed to study whether TCA-induced QTc prolongation is a false-positive observation due to overestimation at high heart rates. For this, we included 12,734 participants from the prospective population-based Rotterdam Study, with a total of 27,068 electrocardiograms (ECGs), of which, 331 during TCA use. Associations between use of TCAs, QTc, and heart rate were studied with linear repeated measurement analyses. QT was corrected for heart rate according to Bazett (QTcBazett), Fridericia (QTcFridericia), or a correction based on regression coefficients obtained from the Rotterdam Study data (QTcStatistical). On ECGs recorded during TCA use, QTcBazett was 6.5 milliseconds (95% confidence interval, 4.0–9.0) longer, and heart rate was 5.8 beats per minute (95% confidence interval, 4.7–6.9) faster than during nonuse. QTcFridericia and QTcStatistical were not statistically significantly longer during TCA use than during nonuse. Furthermore, QTcBazett was similar for ECGs recorded during TCA use and nonuse after statistical adjustment for heart rate. According to our results, TCA use does not seem to be associated with QTc prolongation. Therefore, the current advice of regulatory authorities to restrict the use of these drugs and to do regular checkups of the QTc may need to be revised. Other formulas, like Fridericia’s, might be preferred.