In this paper, a method is presented to analyze the mechanical stress distribution in a pacing lead based on a sequence of paired 2D angiographic images. The 3D positions and geometrical shapes of an implanted pacemaker lead throughout the cardiac cycle were generated using a previously validated 3D modeling technique. Based on the Frenet–Serret formulas, the kinematic property of the lead was derived and characterized. The distribution of curvature and twist angle per unit length in the pacing lead was calculated from a finite difference method, which enabled a rapid and effective computation of the mechanical stress in the pacing lead. The analytical solution of the helix deformation geometry was used to evaluate the accuracy of the proposed numerical method, and an excellent agreement in curvature, twist angle, and stresses was achieved. As demonstrated in the example, the proposed technique can be used to analyze the complex movement and deformation of the implanted pacing lead in vivo. The information can facilitate the future development of pacing leads.