Although cardiac resynchronization therapy (CRT) is an effective treatment for chronic systolic heart failure with dyssynchrony, about one-third of patients do not respond favorably. The interaction between the pacing lead and the coronary sinus (CS) branches is of paramount importance for an effective resynchronization. Minor changes in lead position overtime could interfere with CRT mechanics, without affecting even biophysical parameters or ECG morphology. Although late post-implant CS lead dislodgement rate is consistent, lead movements have been little investigated and only with bi-dimensional methods. The aim of this study was (1) to develop a method for quantifying CS lead position in the 3D domain throughout the cardiac cycle and (2) to test it by comparing the CS lead position at implant and at follow-up, using chest fluoroscopy. Method performance, its accuracy and reproducibility were qualitatively and quantitatively assessed. Intra- and inter-observer percent discordance between trajectories were also computed. The accuracy of the procedure resulted in 0.3 ± 0.1 mm and its resolution was 0.5 mm. Intra- and inter-observer discordances were 2.2 ± 1.5 and 5.5 ± 3.6 mm, respectively. The proposed method for measuring the CS lead dynamic placement in 3D space seems accurate and reproducible. Investigating CS lead 3D dynamics could provide further insights into CRT mechanics.